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Menon U, Gentry-Maharaj A, Burnell M, Ryan A, Kalsi JK, Singh N, Dawnay A, Fallowfield L, McGuire AJ, Campbell S, Skates SJ, Parmar M, Jacobs IJ. Mortality impact, risks, and benefits of general population screening for ovarian cancer: the UKCTOCS randomised controlled trial. Health Technol Assess 2025; 29:1-93. [PMID: 37183782 PMCID: PMC10542866 DOI: 10.3310/bhbr5832] [Citation(s) in RCA: 9] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2023] Open
Abstract
Background Ovarian and tubal cancers are lethal gynaecological cancers, with over 50% of the patients diagnosed at advanced stage. Trial design Randomised controlled trial involving 27 primary care trusts adjacent to 13 trial centres based at NHS Trusts in England, Wales and Northern Ireland. Methods Postmenopausal average-risk women, aged 50-74, with intact ovaries and no previous ovarian or current non-ovarian cancer. Interventions One of two annual screening strategies: (1) multimodal screening (MMS) using a longitudinal CA125 algorithm with repeat CA125 testing and transvaginal scan (TVS) as second line test (2) ultrasound screening (USS) using TVS alone with repeat scan to confirm any abnormality. The control (C) group had no screening. Follow-up was through linkage to national registries, postal follow-up questionnaires and direct communication with trial centres and participants. Objective To assess comprehensively risks and benefits of ovarian cancer screening in the general population. Outcome Primary outcome was death due to ovarian or tubal cancer as assigned by an independent outcomes review committee. Secondary outcomes included incidence and stage at diagnosis of ovarian and tubal cancer, compliance, performance characteristics, harms and cost-effectiveness of the two screening strategies and a bioresource for future research. Randomisation The trial management system confirmed eligibility and randomly allocated participants using computer-generated random numbers to MMS, USS and C groups in a 1:1:2 ratio. Blinding Investigators and participants were unblinded and outcomes review committee was masked to randomisation group. Analyses Primary analyses were by intention to screen, comparing separately MMS and USS with C using the Versatile test. Results 1,243,282 women were invited and 205,090 attended for recruitment between April 2001 and September 2005. Randomised 202,638 women: 50,640 MMS, 50,639 USS and 101,359 C group. Numbers analysed for primary outcome 202,562 (>99.9%): 50,625 (>99.9%) MMS, 50,623 (>99.9%) USS, and 101,314 (>99.9%) C group. Outcome Women in MMS and USS groups underwent 345,570 and 327,775 annual screens between randomisation and 31 December 2011. At median follow-up of 16.3 (IQR 15.1-17.3) years, 2055 women developed ovarian or tubal cancer: 522 (1.0% of 50,625) MMS, 517 (1.0% of 50,623) USS, and 1016 (1.0% of 101314) in C group. Compared to the C group, in the MMS group, the incidence of Stage I/II disease was 39.2% (95% CI 16.1 to 66.9) higher and stage III/IV 10.2% (95% CI -21.3 to 2.4) lower. There was no difference in stage in the USS group. 1206 women died of the disease: 296 (0.6%) MMS, 291 (0.6%) USS, and 619 (0.6%) C group. There was no significant reduction in ovarian and tubal cancer deaths in either MMS (p = 0.580) or USS (p = 0.360) groups compared to the C group. Overall compliance with annual screening episode was 80.8% (345,570/420,047) in the MMS and 78.0% (327,775/420,047) in the USS group. For ovarian and tubal cancers diagnosed within one year of the last test in a screening episode, in the MMS group, the sensitivity, specificity and positive predictive values were 83.8% (95% CI 78.7 to 88.1), 99.8% (95% CI 99.8 to 99.9), and 28.8% (95% CI 25.5 to 32.2) and in the USS group, 72.2% (95% CI 65.9 to 78.0), 99.5% (95% CI 99.5 to 99.5), and 9.1% (95% CI 7.8 to 10.5) respectively. The final within-trial cost-effectiveness analysis was not undertaken as there was no mortality reduction. A bioresource (UKCTOCS Longitudinal Women's Cohort) of longitudinal outcome data and over 0.5 million serum samples including serial annual samples in women in the MMS group was established and to date has been used in many new studies, mainly focused on early detection of cancer. Harms Both screening tests (venepuncture and TVS) were associated with minor complications with low (8.6/100,000 screens MMS; 18.6/100,000 screens USS) complication rates. Screening itself did not cause anxiety unless more intense repeat testing was required following abnormal screens. In the MMS group, for each screen-detected ovarian or tubal cancer, an additional 2.3 (489 false positives; 212 cancers) women in the MMS group had unnecessary false-positive (benign adnexal pathology or normal adnexa) surgery. Overall, 14 (489/345,572 annual screens) underwent unnecessary surgery per 10,000 screens. In the USS group, for each screen-detected ovarian or tubal cancer, an additional 10 (1630 false positives; 164 cancers) underwent unnecessary false-positive surgery. Overall, 50 (1630/327,775 annual screens) women underwent unnecessary surgery per 10,000 screens. Conclusions Population screening for ovarian and tubal cancer for average-risk women using these strategies should not be undertaken. Decreased incidence of Stage III/IV cancers during multimodal screening did not translate to mortality reduction. Researchers should be cautious about using early stage as a surrogate outcome in screening trials. Meanwhile the bioresource provides a unique opportunity to evaluate early cancer detection tests. Funding Long-term follow-up UKCTOCS (2015-2020) - National Institute for Health and Care Research (NIHR HTA grant 16/46/01), Cancer Research UK, and The Eve Appeal. UKCTOCS (2001-2014) - Medical Research Council (MRC) (G9901012/G0801228), Cancer Research UK (C1479/A2884), and the UK Department of Health, with additional support from The Eve Appeal. Researchers at UCL were supported by the NIHR UCL Hospitals Biomedical Research Centre and by MRC Clinical Trials Unit at UCL core funding (MR_UU_12023).
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Affiliation(s)
- Usha Menon
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Aleksandra Gentry-Maharaj
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Matthew Burnell
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Andy Ryan
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Jatinderpal K Kalsi
- Department of Women's Cancer, Institute for Women's Health, University College London, London, UK
- CRUK UCL Centre, UCL Cancer Institute, London, UK
| | - Naveena Singh
- Department of Cellular Pathology, Barts Health NHS Trust, London, UK
| | - Anne Dawnay
- Department of Clinical Biochemistry, Barts Health NHS Service Trust, London, UK
| | - Lesley Fallowfield
- Sussex Health Outcomes Research and Education in Cancer (SHORE-C), Brighton and Sussex Medical School, University of Sussex, Brighton, UK
| | | | | | - Steven J Skates
- Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Mahesh Parmar
- MRC Clinical Trials Unit, Institute of Clinical Trials and Methodology, University College London, London, UK
| | - Ian J Jacobs
- Department of Women's Health, University of New South Wales, Sydney, NSW, Australia
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Le Saux O, McNeish I, D'Incalci M, Narducci F, Ray-Coquard I. Controversies in the management of serous tubal intra-epithelial carcinoma lesions of the fallopian tube. Int J Gynecol Cancer 2025; 35:101667. [PMID: 39987717 DOI: 10.1016/j.ijgc.2025.101667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2024] [Revised: 01/23/2025] [Accepted: 01/24/2025] [Indexed: 02/25/2025] Open
Abstract
High-grade serous carcinoma is the most lethal gynecological malignancy. Although serous tubal intra-epithelial carcinoma is increasingly recognized as a precursor to high-grade serous carcinoma, its optimal management remains controversial. This review examines the controversies in serous tubal intra-epithelial carcinoma pathogenesis, diagnosis, management, and follow-up, highlighting the need for collaboration, standardized guidelines, and further research to improve patient outcomes.
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Affiliation(s)
- Olivia Le Saux
- Department of Medical Oncology, Center Léon Bérard, Lyon, France; Université Claude Bernard Lyon 1, Université de Lyon, Centre Léon Bérard, INSERM 1052-CNRS 5286, Cancer Research Center of Lyon, "Cancer Immune Surveillance and Therapeutic Targeting" Laboratory, Lyon, France.
| | - Iain McNeish
- Department of Surgery and Cancer, Imperial College London, London, United Kingdom
| | - Maurizio D'Incalci
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; IRCCS Humanitas Research Hospital, Laboratory of Cancer Pharmacology, Rozzano, Milan, Italy
| | | | - Isabelle Ray-Coquard
- Department of Medical Oncology, Center Léon Bérard, Lyon, France; University Claude Bernard Lyon I Laboratoire RESHAPE U1290, Lyon, France
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Sonkusare S, Sampige Prasannakumar S, Ahuja V, Kumar R. Unusual recurrence in advanced ovarian cancer after interval cytoreductive surgery and HIPEC. BMJ Case Rep 2025; 18:e262137. [PMID: 39828306 DOI: 10.1136/bcr-2024-262137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2025] Open
Abstract
Ovarian cancer is the second most fatal gynaecological malignancy. The relapses after treatment of ovarian cancer usually occur within 2 years after completion of the first-line therapy. Recurrent ovarian cancer commonly presents as peritoneal surface deposits in the abdomen with or without ascites. A delayed relapse presenting as a solitary lesion in the urinary bladder wall is unusual in patients treated for advanced ovarian cancer. We report the successful management of a case of solitary metastasis of ovarian cancer in the urinary bladder wall, which occurred more than 6 years after achieving a complete remission state.
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Affiliation(s)
- Shipra Sonkusare
- Gynaecological Oncology, Aster Hospitals Inc, Bangalore, Karnataka, India
- Obstetrics & Gynaecology, All India Institute of Medical Sciences - Nagpur, Nagpur, Maharashtra, India
| | | | - Vijay Ahuja
- Gynaecological Oncology, Aster Hospitals Inc, Bangalore, Karnataka, India
| | - Rohit Kumar
- Surgical Oncology, Aster Hospitals Inc, Bangalore, Karnataka, India
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Cheng Y, Li Q, Sun G, Li T, Zou Y, Ye H, Wang K, Shi J, Wang P. Serum anti-CFL1, anti-EZR, and anti-CYPA autoantibody as diagnostic markers in ovarian cancer. Sci Rep 2024; 14:9757. [PMID: 38684875 PMCID: PMC11058243 DOI: 10.1038/s41598-024-60544-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2024] [Accepted: 04/24/2024] [Indexed: 05/02/2024] Open
Abstract
The purpose of this study was to identify novel autoantibodies against tumor-associated antigens (TAAs) and explore a diagnostic panel for Ovarian cancer (OC). Enzyme-linked immunosorbent assay was used to detect the expression of five anti-TAA autoantibodies in the discovery (70 OC and 70 normal controls) and validation cohorts (128 OC and 128 normal controls). Machine learning methods were used to construct a diagnostic panel. Serum samples from 81 patients with benign ovarian disease were used to identify the specificity of anti-TAA autoantibodies for OC. In both the discovery and validation cohorts, the expression of anti-CFL1, anti-EZR, anti-CYPA, and anti-PFN1 was higher in patients with OC than that in normal controls. The area under the receiver operating characteristic curve, sensitivity, and specificity of the panel containing anti-CFL1, anti-EZR, and anti-CYPA were 0.762, 55.56%, and 81.31%. The panel identified 53.06%, 53.33%, and 51.11% of CA125 negative, HE4 negative and the Risk of Ovarian Malignancy Algorithm negative OC patients, respectively. The combination of the three anti-TAA autoantibodies can serve as a favorable diagnostic tool for OC and has the potential to be a complementary biomarker for CA125 and HE4 in the diagnosis of ovarian cancer.
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Affiliation(s)
- Yifan Cheng
- College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan Province, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - Qing Li
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
- School of Basic Medical Sciences, Academy of Medical Science, Zhengzhou University, Zhengzhou, 450052, Henan, China
| | - Guiying Sun
- College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan Province, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - Tiandong Li
- College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan Province, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - Yuanlin Zou
- College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan Province, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - Hua Ye
- College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan Province, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - Keyan Wang
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - Jianxiang Shi
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, 450052, Henan Province, China
| | - Peng Wang
- College of Public Health, Zhengzhou University, Zhengzhou, 450001, Henan Province, China.
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention and Treatment, Zhengzhou University, Zhengzhou, 450052, Henan Province, China.
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Rani S, Lai A, Nair S, Sharma S, Handberg A, Carrion F, Möller A, Salomon C. Extracellular vesicles as mediators of cell-cell communication in ovarian cancer and beyond - A lipids focus. Cytokine Growth Factor Rev 2023; 73:52-68. [PMID: 37423866 DOI: 10.1016/j.cytogfr.2023.06.004] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2023] [Accepted: 06/29/2023] [Indexed: 07/11/2023]
Abstract
Extracellular vesicles (EVs) are messengers that carry information in the form of proteins, lipids, and nucleic acids and are not only essential for intercellular communication but also play a critical role in the progression of various pathologies, including ovarian cancer. There has been recent substantial research characterising EV cargo, specifically, the lipid profile of EVs. Lipids are involved in formation and cargo sorting of EVs, their release and cellular uptake. Numerous lipidomic studies demonstrated the enrichment of specific classes of lipids in EVs derived from cancer cells suggesting that the EV associated lipids can potentially be employed as minimally invasive biomarkers for early diagnosis of various malignancies, including ovarian cancer. In this review, we aim to provide a general overview of the heterogeneity of EV, biogenesis, their lipid content, and function in cancer progression focussing on ovarian cancer.
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Affiliation(s)
- Shikha Rani
- Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, University of Queensland Centre for Clinical Research, Faculty of Medicine, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, QLD 4029, Australia
| | - Andrew Lai
- Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, University of Queensland Centre for Clinical Research, Faculty of Medicine, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, QLD 4029, Australia
| | - Soumya Nair
- Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, University of Queensland Centre for Clinical Research, Faculty of Medicine, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, QLD 4029, Australia
| | - Shayna Sharma
- Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, University of Queensland Centre for Clinical Research, Faculty of Medicine, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, QLD 4029, Australia
| | - Aase Handberg
- Department of Clinical Biochemistry, Aalborg University Hospital, Aalborg, Denmark
| | - Flavio Carrion
- Departamento de Investigación, Postgrado y Educación Continua (DIPEC), Facultad de Ciencias de la Salud, Universidad del Alba, Santiago, Chile
| | - Andreas Möller
- Department of Otorhinolaryngology, Li Ka Shing Institute of Health Sciences, Chinese University of Hong Kong, Shatin, Hong Kong
| | - Carlos Salomon
- Translational Extracellular Vesicles in Obstetrics and Gynae-Oncology Group, University of Queensland Centre for Clinical Research, Faculty of Medicine, Royal Brisbane and Women's Hospital, The University of Queensland, Brisbane, QLD 4029, Australia; Departamento de Investigación, Postgrado y Educación Continua (DIPEC), Facultad de Ciencias de la Salud, Universidad del Alba, Santiago, Chile.
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Zhang R, Siu MKY, Ngan HYS, Chan KKL. Molecular Biomarkers for the Early Detection of Ovarian Cancer. Int J Mol Sci 2022; 23:ijms231912041. [PMID: 36233339 PMCID: PMC9569881 DOI: 10.3390/ijms231912041] [Citation(s) in RCA: 100] [Impact Index Per Article: 33.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 09/30/2022] [Accepted: 10/04/2022] [Indexed: 11/16/2022] Open
Abstract
Ovarian cancer is the deadliest gynecological cancer, leading to over 152,000 deaths each year. A late diagnosis is the primary factor causing a poor prognosis of ovarian cancer and often occurs due to a lack of specific symptoms and effective biomarkers for an early detection. Currently, cancer antigen 125 (CA125) is the most widely used biomarker for ovarian cancer detection, but this approach is limited by a low specificity. In recent years, multimarker panels have been developed by combining molecular biomarkers such as human epididymis secretory protein 4 (HE4), ultrasound results, or menopausal status to improve the diagnostic efficacy. The risk of ovarian malignancy algorithm (ROMA), the risk of malignancy index (RMI), and OVA1 assays have also been clinically used with improved sensitivity and specificity. Ongoing investigations into novel biomarkers such as autoantibodies, ctDNAs, miRNAs, and DNA methylation signatures continue to aim to provide earlier detection methods for ovarian cancer. This paper reviews recent advancements in molecular biomarkers for the early detection of ovarian cancer.
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Liu Z, Wu J, Wang X, Ji X. Multivariate logistic regression analysis of the correlation between five biomarkers and ovarian cancer in patients with intermediate-risk: A prospective cross-sectional study. Front Cell Dev Biol 2022; 10:876071. [PMID: 36120557 PMCID: PMC9470860 DOI: 10.3389/fcell.2022.876071] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2022] [Accepted: 07/18/2022] [Indexed: 11/30/2022] Open
Abstract
Objective: To find potential diagnostic biomarkers for ovarian cancer (OC), a prospective analysis of the expression of five biomarkers in patients with intermediate-risk and their correlation with the occurrence of OC was conducted. Method: A prospective observational study was carried out, patients who underwent surgical treatment with benign or malignant ovarian tumors in our hospital from January 2020 to February 2021 were included in this study, and a total of 263 patients were enrolled. Based on the postoperative pathological results, enrolled patients were divided into ovarian cancer group and benign tumor group (n = 135). The ovarian cancer group was further divided into a mid-stage group (n = 46) and an advanced-stage group (n = 82). The basic information of the three groups of patients was collected, the preoperative imaging data of the patients were collected to assess the lymph node metastasis, the preoperative blood samples were collected to examine cancer antigen 125 (CA125), carbohydrate antigen 19–9 (CA19–9), Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and the postoperative pathological data were sorted and summarized. Result: The average during of disease in the advanced ovarian cancer group was 0.55 ± 0.18 years higher than the benign tumor group (0.43 ± 0.14 years), p < 0.001. In the advanced ovarian cancer group, the ratio of patients with the tumor, node, metastasis (TNM) stage IV (64.63%), with tumor Grade stage II and III (93.90%), and without lymph node metastasis (64.63%) was respectively more than that in the mid-stage group (accordingly 0.00, 36.96, 23.91%) (p < 0.001); The ratio of patients with TNM grade III in the mid-stage group (73.91%) was more than that in the advanced group (35.37%) (p < 0.001). The levels of the five biomarkers: CA19-9, CA125, NLR, PLR, and BDNF were different among the three groups (p < 0.001). Conclusion: CA19-9, CA125, NLR, PLR, BDNF are five biomarkers related to the occurrence of ovarian cancer and are risk factors for it. These five biomarkers and their Combined-Value may be suitable to apply in the diagnosis and the identification of ovarian cancer in patients with intermediate-risk.
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Affiliation(s)
- Zhen Liu
- Department of Nuclear Medicine, Cangzhou Central Hospital, Cangzhou, China
| | - Jingjing Wu
- Department of Laboratory Medicine, Cangzhou Central Hospital, Cangzhou, China
| | - Xiuli Wang
- Department of Laboratory Medicine, Cangzhou Central Hospital, Cangzhou, China
| | - Xiaoyang Ji
- Department of Obstetrics and Gynecology, Ningjin Hospital of Integrated Traditional Chinese and Western Medicine, Xingtai, China
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Management of Hereditary Breast Cancer: An Overview. Breast Cancer 2022. [DOI: 10.1007/978-981-16-4546-4_18] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Pietkiewicz D, Klupczynska-Gabryszak A, Plewa S, Misiura M, Horala A, Miltyk W, Nowak-Markwitz E, Kokot ZJ, Matysiak J. Free Amino Acid Alterations in Patients with Gynecological and Breast Cancer: A Review. Pharmaceuticals (Basel) 2021; 14:ph14080731. [PMID: 34451829 PMCID: PMC8400482 DOI: 10.3390/ph14080731] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2021] [Revised: 07/15/2021] [Accepted: 07/21/2021] [Indexed: 02/06/2023] Open
Abstract
Gynecological and breast cancers still remain a significant health problem worldwide. Diagnostic methods are not sensitive and specific enough to detect the disease at an early stage. During carcinogenesis and tumor progression, the cellular need for DNA and protein synthesis increases leading to changes in the levels of amino acids. An important role of amino acids in many biological pathways, including biosynthesis of proteins, nucleic acids, enzymes, etc., which serve as an energy source and maintain redox balance, has been highlighted in many research articles. The aim of this review is a detailed analysis of the literature on metabolomic studies of gynecology and breast cancers with particular emphasis on alterations in free amino acid profiles. The work includes a brief overview of the metabolomic methodology and types of biological samples used in the studies. Special attention was paid to the possible role of selected amino acids in the carcinogenesis, especially proline and amino acids related to its metabolism. There is a clear need for further research and multiple external validation studies to establish the role of amino acid profiling in diagnosing gynecological and breast cancers.
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Affiliation(s)
- Dagmara Pietkiewicz
- Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-780 Poznan, Poland; (D.P.); (A.K.-G.); (S.P.)
| | - Agnieszka Klupczynska-Gabryszak
- Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-780 Poznan, Poland; (D.P.); (A.K.-G.); (S.P.)
| | - Szymon Plewa
- Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-780 Poznan, Poland; (D.P.); (A.K.-G.); (S.P.)
| | - Magdalena Misiura
- Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, 15-089 Bialystok, Poland; (M.M.); (W.M.)
| | - Agnieszka Horala
- Gynecologic Oncology Department, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (A.H.); (E.N.-M.)
| | - Wojciech Miltyk
- Department of Analysis and Bioanalysis of Medicines, Medical University of Bialystok, 15-089 Bialystok, Poland; (M.M.); (W.M.)
| | - Ewa Nowak-Markwitz
- Gynecologic Oncology Department, Poznan University of Medical Sciences, 61-701 Poznan, Poland; (A.H.); (E.N.-M.)
| | - Zenon J. Kokot
- Faculty of Health Sciences, Calisia University, 62-800 Kalisz, Poland;
| | - Jan Matysiak
- Department of Inorganic and Analytical Chemistry, Poznan University of Medical Sciences, 60-780 Poznan, Poland; (D.P.); (A.K.-G.); (S.P.)
- Correspondence:
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Wang YS, Ren SF, Jiang W, Lu JQ, Zhang XY, Li XP, Cao R, Xu CJ. CA125-Tn ELISA assay improves specificity of pre-operative diagnosis of ovarian cancer among patients with elevated serum CA125 levels. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:788. [PMID: 34268401 PMCID: PMC8246179 DOI: 10.21037/atm-20-8053] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/18/2020] [Accepted: 02/26/2021] [Indexed: 12/28/2022]
Abstract
Background CA125 is the most widely used serum marker for preoperative diagnosis of ovarian cancer. However, CA125 elevation is not specific to ovarian cancer. More than 60% of patients who have elevated CA125 levels do not have ovarian cancer. To overcome the low specificity of CA125, we identified a CA125 glycoform that was specifically elevated in ovarian cancer and that may help in the further triage of patients with elevated serum CA125 levels. Methods We used antibody-lectin ELISA to detect various CA125 glycoforms. Among 21 lectins tested, VVA, a plant lectin that preferentially binds Tn antigen, showed significantly stronger binding with ovarian cancer-derived CA125 than benign condition-derived CA125. CA125-Tn levels were tested among patients with elevated CA125 levels (n=328, including 68 ovarian cancer, 15 ovarian borderline tumors, and 245 benign conditions). The efficacy of CA125-Tn in diagnosing ovarian cancer was evaluated using ROC analysis. Results Medians and 25th to 75th quartiles of CA125-Tn levels were 0.31 (0.18–0.65) in ovarian cancer, 0.07 (0.02–0.12) in ovarian borderline tumor, and 0.07 (0.01–0.12) in benign conditions. AUC of the ROC curve was 0.890 (95% CI: 0.845, 0.935) for CA125-Tn to discriminate ovarian cancer cases from nonmalignant cases (borderline tumors and benign conditions). Its performance was even better among patients older than 45 y (AUC: 0.905, 95% CI: 0.841, 0.969). Specificity was improved from 35.1% for CA125 to 75.7% for CA125-Tn among patients older than 45 y when sensitivity was fixed at 90%. Conclusions CA125-Tn ELISA assay can improve specificity of the preoperative diagnosis of ovarian cancer and serve as a further triage strategy for patients with elevated CA125 levels.
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Affiliation(s)
- Yi-Sheng Wang
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Shi-Fang Ren
- Key Laboratory of Glycoconjugate Research Ministry of Public Health, Shanghai, China.,Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China
| | - Wei Jiang
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Jia-Qi Lu
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Xiao-Yan Zhang
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China
| | - Xiao-Ping Li
- Peking University People's Hospital, Beijing, China
| | - Rui Cao
- Dalian Obstetrics & Gynecology Hospital, Liaoning, China
| | - Cong-Jian Xu
- Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China.,Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, China.,Institute of Biomedical Sciences, Fudan University, Shanghai, China.,Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, China
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11
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Kalsi J, Gentry-Maharaj A, Ryan A, Singh N, Burnell M, Massingham S, Apostolidou S, Sharma A, Williamson K, Seif M, Mould T, Woolas R, Dobbs S, Leeson S, Fallowfield L, Skates SJ, Parmar M, Campbell S, Jacobs I, McGuire A, Menon U. Performance Characteristics of the Ultrasound Strategy during Incidence Screening in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Cancers (Basel) 2021; 13:cancers13040858. [PMID: 33670571 PMCID: PMC7922843 DOI: 10.3390/cancers13040858] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 02/04/2021] [Accepted: 02/09/2021] [Indexed: 11/16/2022] Open
Abstract
Randomised controlled trials of ovarian cancer (OC) screening have not yet demonstrated an impact on disease mortality. Meanwhile, the screening data from clinical trials represents a rich resource to understand the performance of modalities used. We report here on incidence screening in the ultrasound arm of UKCTOCS. 44,799 of the 50,639 women who were randomised to annual screening with transvaginal ultrasound attended annual incidence screening between 28 April 2002 and 31 December 2011. Transvaginal ultrasound was used both as the first and the second line test. Participants were followed up through electronic health record linkage and postal questionnaires. Out of 280,534 annual incidence screens, 960 women underwent screen-positive surgery. 113 had ovarian/tubal cancer (80 invasive epithelial). Of the screen-detected invasive epithelial cancers, 37.5% (95% CI: 26.9-49.0) were Stage I/II. An additional 52 (50 invasive epithelial) were diagnosed within one year of their last screen. Of the 50 interval epithelial cancers, 6.0% (95% CI: 1.3-16.5) were Stage I/II. For detection of all ovarian/tubal cancers diagnosed within one year of screen, the sensitivity, specificity, and positive predictive values were 68.5% (95% CI: 60.8-75.5), 99.7% (95% CI: 99.7-99.7), and 11.8% (95% CI: 9.8-14) respectively. When the analysis was restricted to invasive epithelial cancers, sensitivity, specificity and positive predictive values were 61.5% (95% CI: 52.6-69.9); 99.7% (95% CI: 99.7-99.7) and 8.3% (95% CI: 6.7-10.3), with 12 surgeries per screen positive. The low sensitivity coupled with the advanced stage of interval cancers suggests that ultrasound scanning as the first line test might not be suitable for population screening for ovarian cancer. Trial registration: ISRCTN22488978. Registered on 6 April 2000.
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Affiliation(s)
- Jatinderpal Kalsi
- Department of Women’s Cancer, Institute for Women’s Health, University College London, London WC1E 6HU, UK; (J.K.); (I.J.)
| | - Aleksandra Gentry-Maharaj
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK; (A.G.-M.); (A.R.); (M.B.); (S.M.); (S.A.); (M.P.)
| | - Andy Ryan
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK; (A.G.-M.); (A.R.); (M.B.); (S.M.); (S.A.); (M.P.)
| | - Naveena Singh
- Department of Pathology, Barts and the London, London E1 2ES, UK;
| | - Matthew Burnell
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK; (A.G.-M.); (A.R.); (M.B.); (S.M.); (S.A.); (M.P.)
| | - Susan Massingham
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK; (A.G.-M.); (A.R.); (M.B.); (S.M.); (S.A.); (M.P.)
| | - Sophia Apostolidou
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK; (A.G.-M.); (A.R.); (M.B.); (S.M.); (S.A.); (M.P.)
| | - Aarti Sharma
- Department of Obstetrics and Gynaecology, University Hospital of Wales, Cardiff CF14 4XW, UK;
| | - Karin Williamson
- Department of Gynaecological Oncology, Nottingham City Hospital, Nottingham NG5 1PB, UK;
| | - Mourad Seif
- Division of Gynaecology and of Cancer Services, St. Mary’s Hospital and University of Manchester, Manchester M13 9WL, UK;
| | - Tim Mould
- Department of Gynaecological Oncology, University College Hospital, London NW1 2BU, UK;
| | - Robert Woolas
- Department of Gynaecological Oncology, Queen Alexandra Hospital, Portsmouth PO6 3LY, UK;
| | - Stephen Dobbs
- Department of Gynaecological Oncology, Belfast City Hospital, Belfast BT9 7AB, UK;
| | - Simon Leeson
- Department of Obstetrics and Gynaecology, Ysbyty Gwynedd, Bangor, Gwynedd LL57 2PW, UK;
| | - Lesley Fallowfield
- Cancer Research UK Sussex Psychosocial Oncology Group at Brighton & Sussex Medical School, University of Sussex, Falmer BN1 9PX, UK;
| | - Steven J. Skates
- Massachusetts General Hospital, Harvard Medical School, Boston, MA 02115, USA;
| | - Mahesh Parmar
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK; (A.G.-M.); (A.R.); (M.B.); (S.M.); (S.A.); (M.P.)
| | | | - Ian Jacobs
- Department of Women’s Cancer, Institute for Women’s Health, University College London, London WC1E 6HU, UK; (J.K.); (I.J.)
- Department of Women’s Health, University of New South Wales, Australia, Sydney 2052, Australia
| | - Alistair McGuire
- London School of Economics and Political Science, London WC2A 2AE, UK;
| | - Usha Menon
- MRC Clinical Trials Unit at UCL, Institute of Clinical Trials & Methodology, London WC1V 6LJ, UK; (A.G.-M.); (A.R.); (M.B.); (S.M.); (S.A.); (M.P.)
- Correspondence: ; Tel.: +44-7670-4909
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12
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Shanbhogue KP, Prasad AS, Ucisik-Keser FE, Katabathina VS, Morani AC. Hereditary ovarian tumour syndromes: current update on genetics and imaging. Clin Radiol 2021; 76:313.e15-313.e26. [PMID: 33353730 DOI: 10.1016/j.crad.2020.11.116] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Accepted: 11/20/2020] [Indexed: 01/30/2023]
Abstract
Hereditary ovarian tumour syndromes are a diverse group of hereditary syndromes characterised by the development of specific histotypes of ovarian neoplasms. While BRCA syndromes are exclusively associated with high-grade serous carcinomas, patients with Lynch syndrome show a preponderance of endometrioid subtype of ovarian and endometrial carcinomas. Distinct non-epithelial phenotypes, such as sex cord stromal tumours with annular tubules, Sertoli-Leydig cell tumours, and small cell carcinoma of the hypercalcaemic type occur in patients with Peutz-Jeghers, DICER1, and rhabdoid tumour predisposition syndromes, respectively. Gorlin-Goltz syndrome is characterised by the development of bilateral, multiple ovarian fibromas in 14-24% of patients. Ovarian steroid cell tumours and broad ligament papillary cystadenomas are characteristically found in women with von Hippel-Lindau syndrome. Recent studies have allowed the characterisation of tumour genetics and associated oncological pathways that contribute to tumourigenesis. Implications of the diagnosis of these syndromes on screening, management, and prognosis are discussed.
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Affiliation(s)
- K P Shanbhogue
- Department of Radiology at NYU Grossman School of Medicine, NY 10016, USA
| | - A S Prasad
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX 77030, USA
| | - F E Ucisik-Keser
- Department of Radiology, The University of Texas Health Science Center at Houston, 7000 Fannin St, Houston, TX 77030, USA
| | - V S Katabathina
- Department of Radiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
| | - A C Morani
- Department of Radiology, The University of Texas MD Anderson Cancer Center, 1515 Holocombe Blvd, Houston, TX 77030, USA.
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13
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Clinical relevance of routine transvaginal ultrasound in women referred with pelvic organ prolapse. BMC WOMENS HEALTH 2021; 21:26. [PMID: 33441123 PMCID: PMC7805096 DOI: 10.1186/s12905-021-01173-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/08/2019] [Accepted: 01/04/2021] [Indexed: 11/30/2022]
Abstract
Background The aim of this study was to investigate the prevalence of incidental findings on transvaginal ultrasound scan in women referred with pelvic organ prolapse by a general practitioner and to investigate which further examinations and treatments were performed as a result of these findings. Methods This was a retrospective cohort study that investigated women with pelvic organ prolapse referred to the outpatient urogynaecological clinics at Randers Regional Hospital and Aarhus University Hospital, Denmark. Results A total of 521 women were included and all of them were examined with a routine transvaginal ultrasound scan and a gynaecological examination. Prolapse symptoms only and no specific indication for transvaginal ultrasound scan were seen in 507 women (97.3%), while 14 women (2.7%) received scans on indication. Among the latter women, five (35.7%) had cancer. In the women with solely prolapse symptoms, 59 (11.6%) had incidental findings on transvaginal ultrasound scan, but all were benign. However, two patients were later diagnosed with cancer unrelated to the initial ultrasound findings. The treatment was extended with further examinations not related to POP in 19 of the women (32.2%) with incidental ultrasound findings. Conclusion The prevalence of incidental ultrasound findings was not high in the women referred with pelvic organ prolapse and no additional symptoms, and all these findings were benign. However, it should be considered that these findings resulted in further investigations and changes to the patients’ initial treatment plans. A meticulous anamnesis and digital vaginal examination are crucial to rule out the need for vaginal ultrasound.
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14
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Ma Y, Wang X, Qiu C, Qin J, Wang K, Sun G, Jiang D, Li J, Wang L, Shi J, Wang P, Ye H, Dai L, Jiang BH, Zhang J. Using protein microarray to identify and evaluate autoantibodies to tumor-associated antigens in ovarian cancer. Cancer Sci 2020; 112:537-549. [PMID: 33185955 PMCID: PMC7894002 DOI: 10.1111/cas.14732] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 11/06/2020] [Accepted: 11/08/2020] [Indexed: 12/16/2022] Open
Abstract
The aim of this study was to develop a noninvasive serological diagnostic approach in identifying and evaluating a panel of candidate autoantibodies to tumor‐associated antigens (TAAs) based on protein microarray technology for early detection of ovarian cancer (OC). Protein microarray based on 154 proteins encoded by 138 cancer driver genes was used to screen candidate anti‐TAA autoantibodies in a discovery cohort containing 17 OC and 27 normal controls (NC). Indirect enzyme‐linked immunosorbent assay (ELISA) was used to detect the content of candidate anti‐TAA autoantibodies in sera from 140 subjects in the training cohort. Differential anti‐TAA autoantibodies were further validated in the validation cohort with 328 subjects. Subsequently, 112 sera from the patients with ovarian benign diseases with 104 OC sera and 104 NC sera together were recruited to identify the specificity of representative autoantibodies to OC among ovarian diseases. Five TAAs (GNAS, NPM1, FUBP1, p53, and KRAS) were screened out in the discovery phase, in which four of them presented higher levels in OC than controls (P < .05) in the training cohort, which was consistent with the result in the subsequent validation cohort. An optimized panel of three anti‐TAA (GNAS, p53, and NPM1) autoantibodies was identified to have relatively high sensitivity (51.2%), specificity (86.0%), and accuracy (68.6%), respectively. This panel can identify 51% of OC patients with CA125 negative. This study supports our assumption that anti‐TAA autoantibodies can be considered as potential diagnostic biomarkers for detection of OC; especially a panel of three anti‐TAA autoantibodies could be a good tool in immunodiagnosis of OC.
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Affiliation(s)
- Yan Ma
- Department of Epidemiology and Health Statistics & Henan Key Laboratory of Tumor Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China.,Laboratory of Molecular Biology, Henan Luoyang Orthopedic Hospital & Henan Provincial Orthopedic Institute, Zhengzhou, China
| | - Xiao Wang
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.,Department of Pathology, The University of Iowa, Iowa City, IA, USA
| | - Cuipeng Qiu
- Department of Epidemiology and Health Statistics & Henan Key Laboratory of Tumor Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Jiejie Qin
- Department of Epidemiology and Health Statistics & Henan Key Laboratory of Tumor Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Keyan Wang
- Department of Epidemiology and Health Statistics & Henan Key Laboratory of Tumor Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Guiying Sun
- Department of Epidemiology and Health Statistics & Henan Key Laboratory of Tumor Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Di Jiang
- Department of Epidemiology and Health Statistics & Henan Key Laboratory of Tumor Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Jitian Li
- Laboratory of Molecular Biology, Henan Luoyang Orthopedic Hospital & Henan Provincial Orthopedic Institute, Zhengzhou, China
| | - Lin Wang
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.,Department of Pathology, The University of Iowa, Iowa City, IA, USA
| | - Jianxiang Shi
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Peng Wang
- Department of Epidemiology and Health Statistics & Henan Key Laboratory of Tumor Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Hua Ye
- Department of Epidemiology and Health Statistics & Henan Key Laboratory of Tumor Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China
| | - Liping Dai
- Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
| | - Bing-Hua Jiang
- Department of Pathology, The University of Iowa, Iowa City, IA, USA
| | - Jianying Zhang
- Department of Epidemiology and Health Statistics & Henan Key Laboratory of Tumor Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China.,Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China
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15
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Liu L, Cai L, Liu C, Yu S, Li B, Pan L, Zhao J, Zhao Y, Li W, Yan X. Construction and Validation of a Novel Glycometabolism-Related Gene Signature Predicting Survival in Patients With Ovarian Cancer. Front Genet 2020; 11:585259. [PMID: 33281878 PMCID: PMC7689371 DOI: 10.3389/fgene.2020.585259] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2020] [Accepted: 10/19/2020] [Indexed: 12/22/2022] Open
Abstract
Among all fatal gynecological malignant tumors, ovarian cancer has the highest mortality rate. The purpose of this study was to develop a stable and personalized glycometabolism-related prognostic signature to predict the overall survival of ovarian cancer patients. The gene expression profiles and clinical information of ovarian cancer patients were derived from four public GEO datasets, which were divided into training and testing cohorts. Glycometabolism-related genes significantly associated with prognosis were selected. A risk score model was established and validated to evaluate its predictive value. We found 5 genes significantly related to prognosis and established a five-mRNA signature. The five-mRNA signature significantly divided patients into a low-risk group and a high-risk group in the training set and validation set. Survival analysis showed that high risk scores obtained by the model were significantly correlated with adverse survival outcomes and could be regarded as an independent predictor for patients with ovarian cancer. In addition, the five-mRNA signature can predict the overall survival of ovarian cancer patients in different subgroups. In summary, we successfully constructed a model that can predict the prognosis of patients with ovarian cancer, which provides new insights into postoperative treatment strategies, promotes individualized therapy, and provides potential new targets for immunotherapy.
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Affiliation(s)
- Lixiao Liu
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Luya Cai
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Chuan Liu
- Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
| | - Shanshan Yu
- Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Bingxin Li
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Luyao Pan
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jinduo Zhao
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Ye Zhao
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Wenfeng Li
- Department of Chemoradiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Xiaojian Yan
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
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16
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An Update on Screening and Prevention for Breast and Gynecological Cancers in Average and High Risk Individuals. Am J Med Sci 2020; 360:489-510. [DOI: 10.1016/j.amjms.2020.06.008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2020] [Revised: 05/22/2020] [Accepted: 06/03/2020] [Indexed: 11/21/2022]
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17
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Ning L, Wang L, Zhang H, Jiao X, Chen D. Eukaryotic translation initiation factor 5A in the pathogenesis of cancers. Oncol Lett 2020; 20:81. [PMID: 32863914 PMCID: PMC7436936 DOI: 10.3892/ol.2020.11942] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Accepted: 06/10/2020] [Indexed: 12/11/2022] Open
Abstract
Cancer is the leading cause of death worldwide. The absence of obvious symptoms and insufficiently sensitive biomarkers in early stages of carcinoma limits early diagnosis. Cancer therapy agents and targeted therapy have been used extensively against tissues or organs of specific cancers. However, the intrinsic and/or acquired resistance to the agents or targeted drugs as well as the serious toxic side effects of the drugs would limit their use. Therefore, identifying biomarkers involved in tumorigenesis and progression represents a challenge for cancer diagnosis and therapeutic strategy development. The eukaryotic translation factor 5A (eIF5A), originally identified as an initiation factor, was later shown to promote translation elongation of iterated proline sequences. There are two eIF5A isoforms (eIF5A1 and eIF5A2). eIF5A2 protein consists of 153 residues, and shares 84% amino acid identity with eIF5A1. However, the biological functions of these two isoforms may be significantly different. Recently, it was demonstrated that eIF5Ais widely involved in the pathogenesis of a number of diseases, including cancers. In particular, eIF5A plays an important role in regulating tumor growth, invasion, metastasis and tumor microenvironment. It was also shown to serve as a potential biomarker and target for the diagnosis and treatment of cancers. The present review briefly discusses the latest findings of eIF5A in the pathogenesis of certain malignant cancers and evolving clinical applications.
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Affiliation(s)
- Liang Ning
- Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Lei Wang
- Department of Thyroid Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Honglai Zhang
- Department of Thyroid Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Xuelong Jiao
- Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
| | - Dong Chen
- Department of General Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China
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18
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Periyasamy A, Gopisetty G, Subramanium MJ, Velusamy S, Rajkumar T. Identification and validation of differential plasma proteins levels in epithelial ovarian cancer. J Proteomics 2020; 226:103893. [DOI: 10.1016/j.jprot.2020.103893] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2019] [Revised: 06/24/2020] [Accepted: 06/28/2020] [Indexed: 01/09/2023]
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Survival of Women With Type I and II Epithelial Ovarian Cancer Detected by Ultrasound Screening. Obstet Gynecol 2019; 132:1091-1100. [PMID: 30303916 DOI: 10.1097/aog.0000000000002921] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
OBJECTIVE To estimate the effect of ultrasound screening on stage at detection and long-term disease-specific survival of at-risk women with epithelial ovarian cancer. METHODS Eligibility included all asymptomatic women 50 years of age or older and women 25 years of age or older with a documented family history of ovarian cancer. From 1987 to 2017, 46,101 women received annual ultrasound screening in a prospective cohort trial. Women with a persisting abnormal screen underwent tumor morphology indexing, serum biomarker analysis, and surgery. RESULTS Seventy-one invasive epithelial ovarian cancers and 17 epithelial ovarian tumors of low malignant potential were detected. No women with a low malignant potential tumor experienced recurrent disease. Stage distribution for screen-detected invasive epithelial ovarian cancers was stage I-30 (42%), stage II-15 (21%), stage III-26 (37%), and stage IV-0 (0%). Follow-up varied from 9.2 months to 27 years (mean 7.9 years). Disease-specific survival at 5, 10, and 20 years for women with invasive epithelial ovarian cancer detected by screening was 86±4%, 68±7%, and 65±7%, respectively, vs 45±2%, 31±2%, and 19±3%, respectively, for unscreened women with clinically detected ovarian cancer from the same geographic area who were treated at the same institution by the same treatment protocols (P<.001). Twenty-seven percent of screen-detected malignancies were type I and 73% were type II. The disease-specific survival of women with type I and type II screen-detected tumors was significantly higher than that of women with clinically detected type I and type II tumors and was related directly to earlier stage at detection. CONCLUSION Annual ultrasound screening of at-risk asymptomatic women was associated with lower stage at detection and increased 5-, 10-, and 20-year disease-specific survival of women with both type I and type II epithelial ovarian cancer. CLINICAL TRIAL REGISTRATION OnCore Clinical Trials Management System, NCI-2013-01954.
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20
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Rausei S, Uccella S, D'Alessandro V, Gisone B, Frattini F, Lianos G, Rovera F, Boni L, Dionigi G, Ghezzi F. Aggressive surgery for advanced ovarian cancer performed by a multidisciplinary team: A retrospective analysis on a large series of patients. Surg Open Sci 2019; 1:43-47. [PMID: 32754692 PMCID: PMC7391894 DOI: 10.1016/j.sopen.2019.05.005] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2018] [Revised: 05/09/2019] [Accepted: 05/09/2019] [Indexed: 10/26/2022] Open
Abstract
Background To evaluate the impact of extended surgical treatment performed by a team of gynecologists and general surgeons on postoperative morbidity and survival of patients with advanced ovarian cancer. Methods We collected data of 156 patients with advanced ovarian cancer stage IIb-III-IV according to International Federation of Gynecology and Obstetrics classification and treated with primary cytoreduction. End points were perioperative and postoperative complications and cancer-related survival. Results In 51 cases (51/156, 32.7%) a multivisceral resection was completed. Postoperative complications occurred in 52 cases (33.3%). The duration of the surgical procedure as well as the need for diaphragmatic peritonectomy were the factors independently associated with the development of postoperative complications. Five-year cancer-related survival rate was of 50.7%: only histotype and residual tumor resulted significantly associated. Conclusions Our results highlight the importance of a team of gynecologists and general surgeons with specific interests and skills to achieve cytoreduction as rapidly as possible, even when it implies very complex maneuvers.
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Affiliation(s)
- Stefano Rausei
- Department of Surgery, ASST Valle Olona, Gallarate (VA), Italy
| | - Stefano Uccella
- Department of Obstetrics and Gynecology, Ospedale degli Infermi, Biella, Italy
| | | | - Baldo Gisone
- Department of Gynecology, ASST Settelaghi, University of Insubria, Varese, Italy
| | - Francesco Frattini
- Department of Surgery, ASST Settelaghi, University of Insubria, Varese, Italy
| | | | - Francesca Rovera
- Department of Surgery, ASST Settelaghi, University of Insubria, Varese, Italy
| | - Luigi Boni
- Department of Surgery, IRCCS Ca' Granda - Policlinico Hospital, University of Milan, Milan, Italy
| | - Gianlorenzo Dionigi
- Department of Human Pathology in Adulthood and Childhood, University of Messina, Messina, Italy
| | - Fabio Ghezzi
- Department of Gynecology, ASST Settelaghi, University of Insubria, Varese, Italy
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21
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ACOG Committee Opinion No. 774: Opportunistic Salpingectomy as a Strategy for Epithelial Ovarian Cancer Prevention. Obstet Gynecol 2019; 133:e279-e284. [DOI: 10.1097/aog.0000000000003164] [Citation(s) in RCA: 60] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
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22
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Mubarak AI, Morani AC, Samuel J, Sun J, Wei W, Bhosale P. Can Presurgical Ultrasound Predict Survival in Women With Ovarian Masses? Ultrasound Q 2019; 35:39-44. [PMID: 30516730 PMCID: PMC11864591 DOI: 10.1097/ruq.0000000000000401] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE This study aimed to determine the ability of ultrasound to predict survival and detect more aggressive tumors in women with ovarian masses. MATERIALS AND METHODS Institutional review board approval was obtained. A total of 167 patients who presented with adnexal mass/masses were included. These were documented as benign or malignant on ultrasound. Age, date of diagnosis and date of death, type of tumor, and tumor marker cancer antigen 125 (CA-125) values were recorded. A CA-125 value of less than 35 U/mL was considered normal. All cases underwent surgery. Pathologic findings were considered as reference standard. The 2 × 2 cross-tabulations were used to correlate dichotomized CA-125, US diagnosis (benign vs malignant), and pathologic status. Difference of distributions was tested using the Wilcoxon rank sum test, and their association was tested using the Fisher exact test. All tests were 2-sided, and P values of 0.05 or less were considered statistically significant. Kaplan-Meir curves were generated to estimate survival. RESULTS There was a statistically significant difference in patients with benign versus malignant tumors based on pathology (P < 0.0001) and ultrasound (P < 0.0003). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of ultrasound were 55%, 86%, 90% and 46%, and 81%. Patients diagnosed as having malignant tumors based on ultrasound had statistically significant worse overall survival. Probability of survival based on pathologic diagnosis of malignancy was statistically significant at P < 0.0003; based on ultrasound, P < 0.0001; and based on CA-125, P < 0.041. CONCLUSION Patients who had ultrasound-based prediction of ovarian malignancy had overall worse survival probability (P < 0.0001) compared with CA-125- or pathology-based prediction.
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Affiliation(s)
- Ahmad Iyad Mubarak
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Ajaykumar C Morani
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Jessica Samuel
- University of California at Los Angeles, Los Angeles, CA, United States
| | - Jia Sun
- Department of Biotatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Wei Wei
- Department of Biotatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Priya Bhosale
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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Evaluation of Microscopic Changes in Fallopian Tubes of BRCA Mutation Carriers by Morphometric Analysis of Histologic Slides: A Preliminary Pilot Study. Int J Gynecol Pathol 2018; 37:460-467. [PMID: 28863070 DOI: 10.1097/pgp.0000000000000440] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
Mutations in BRCA genes increase the risk of ovarian cancer, yet no method for early diagnosis is available. Some serous ovarian tumors are hypothesized to stem from cells of the fallopian tube fimbria. Using a novel method of computerized morphometry of the fimbrial epithelium, this study aimed to detect morphologic differences in noncancerous fimbriae between BRCA mutation carriers and noncarriers, and between healthy and serous ovarian cancer patients. Twenty-four fimbriae from healthy women (13 BRCA+, 11 BRCA-) and 21 fimbriae from women with serous ovarian cancer (10 BRCA+, 11 BRCA-), all reported as "normal" by hematoxylin and eosin examination, were subjected to computerized histomorphometric analysis. A Fast Fourier Transformation was applied to images of fimbrial epithelium and the Fast Fourier Transformation 2-dimensional frequency maps were subsequently quantified for nuclear orientation and planar distribution by a cooccurrence matrix analysis. Additional analysis of nuclear contour was applied to the fimbriae of the healthy women. Among the healthy women, significant differences were found in morphometric characteristics between the BRCA mutation carriers and noncarriers. Among the women with ovarian cancer, no significant differences were found between BRCA mutation carriers and noncarriers. Between healthy women and those with ovarian cancer, significant differences were detected, regardless of BRCA mutational status. A novel method, which combined Fast Fourier Transformation with cooccurrence matrix analysis, demonstrated differences in morphometric characteristics in the fimbriae between healthy and ovarian cancer patients, and between BRCA mutation carriers and noncarriers. The clinical significance of these observations should be investigated.
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24
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Moorman PG, Barrett NJ, Wang F, Alberg JA, Bandera EV, Barnholtz-Sloan JB, Bondy M, Cote ML, Funkhouser E, Kelemen LE, Peres LC, Peters ES, Schwartz AG, Terry PD, Crankshaw S, Abbott SE, Schildkraut JM. Effect of Cultural, Folk, and Religious Beliefs and Practices on Delays in Diagnosis of Ovarian Cancer in African American Women. J Womens Health (Larchmt) 2018; 28:444-451. [PMID: 30481095 DOI: 10.1089/jwh.2018.7031] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
BACKGROUND Certain cultural, folk, and religious beliefs that are more common among African Americans (AAs) have been associated with later-stage breast cancer. It is unknown if these beliefs are similarly associated with delays in diagnosis of ovarian cancer. METHODS Data from a multicenter case-control study of ovarian cancer in AA women were used to examine associations between cultural/folk beliefs and religious practices and stage at diagnosis and symptom duration before diagnosis. Associations between cultural/folk beliefs or religious practices and stage at diagnosis were assessed with logistic regression analyses, and associations with symptom duration with linear regression analyses. RESULTS Agreement with several of the cultural/folk belief statements was high (e.g., 40% agreed that "if a person prays about cancer, God will heal it without medical treatments"), and ∼90% of women expressed moderate to high levels of religiosity/spirituality. Higher levels of religiosity/spirituality were associated with a twofold increase in the odds of stage III-IV ovarian cancer, whereas agreement with the cultural/folk belief statements was not associated with stage. Symptom duration before diagnosis was not consistently associated with cultural/folk beliefs or religiosity/spirituality. CONCLUSIONS Women who reported stronger religious beliefs or practices had increased odds of higher stage ovarian cancer. Inaccurate cultural/folk beliefs about cancer treament were not associated with stage; however, these beliefs were highly prevalent in our population and could impact patient treatment decisions. Our findings suggest opportunities for health education interventions, especially working with churches, and improved doctor-patient communication.
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Affiliation(s)
- Patricia G Moorman
- 1 Department of Community and Family Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina
| | - Nadine J Barrett
- 1 Department of Community and Family Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina
| | - Frances Wang
- 1 Department of Community and Family Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina
| | - J Anthony Alberg
- 2 Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, South Carolina
| | - Elisa V Bandera
- 3 Department of Population Science, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - J B Barnholtz-Sloan
- 4 Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Melissa Bondy
- 5 Cancer Prevention and Population Sciences Program, Baylor College of Medicine, Houston, Texas
| | - Michele L Cote
- 6 Department of Oncology, Karmanos Cancer Institute Population Studies and Disparities Research Program, Wayne State University School of Medicine, Detroit, Michigan
| | - Ellen Funkhouser
- 7 Division of Preventive Medicine, University of Alabama-Birmingham, Birmingham, Alabama
| | - Linda E Kelemen
- 8 Department of Public Health Sciences, Hollings Cancer Center, Medical University of South Carolina, Charleston, South Carolina
| | | | - Edwards S Peters
- 10 Epidemiology Program, Louisiana State University Health Sciences Center School of Public Health, New Orleans, Louisiana
| | - A G Schwartz
- 6 Department of Oncology, Karmanos Cancer Institute Population Studies and Disparities Research Program, Wayne State University School of Medicine, Detroit, Michigan
| | - Paul D Terry
- 11 Department of Medicine, University of Tennessee Graduate School of Medicine, Knoxville, Tennessee
| | - Sydnee Crankshaw
- 1 Department of Community and Family Medicine, Duke Cancer Institute, Duke University, Durham, North Carolina
| | - Sarah E Abbott
- 12 Hunter Holmes McGuire Veterans Affairs Medical Center, Richmond, Virginia
| | - Joellen M Schildkraut
- 13 Department of Public Health Sciences, University of Virginia, Charlottesville, Virginia
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25
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Bell RJ, Davis SR. Routine Screening for Urinary Incontinence in Women: Caution Advised. Ann Intern Med 2018; 169:345-346. [PMID: 30105377 DOI: 10.7326/m18-1768] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Affiliation(s)
- Robin J Bell
- Monash University, Melbourne, Victoria, Australia (R.J.B., S.R.D.)
| | - Susan R Davis
- Monash University, Melbourne, Victoria, Australia (R.J.B., S.R.D.)
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26
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Hereditary Cancers in Gynecology: What Physicians Should Know About Genetic Testing, Screening, and Risk Reduction. Obstet Gynecol Clin North Am 2018; 45:155-173. [PMID: 29428283 DOI: 10.1016/j.ogc.2017.10.011] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Obstetrician gynecologists play a critical role in the identification of women who may carry a germline mutation placing them at an increased lifetime risk of gynecologic and nongynecologic cancers. Given this, all gynecologists must have a basic understanding of the most common hereditary cancer syndromes, the associated cancer risks, and possible risk-reducing interventions to play a proactive role in the care of these women. This article presents general guidelines and potential tools for identification of high-risk patients, reviews the current literature regarding genetic mutations associated with gynecologic malignancies, and proposes screening and risk-reduction options for high-risk patients.
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27
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Davidson T, Komisar O, Korach J, Felder S, Apter S, Ben-Haim S, Perri T. Physiologic uptake of 18F-FDG in transposed ovaries may mimic metastasis on 18F-FDG PET/CT imaging. Nucl Med Commun 2018; 39:171-178. [PMID: 29215392 DOI: 10.1097/mnm.0000000000000785] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
BACKGROUND Ovarian transposition is aimed at preserving ovarian function before irradiation in pelvic malignancies. The extrapelvic location of the ovaries and their physiologic fluorine-18-fluorodeoxyglucose (F-FDG)-uptake is a potential source of misdiagnosis as metastasis on F-FDG PET/CT. We describe the F-FDG PET/CT characteristics of transposed ovaries and their changes over time. PATIENTS AND METHODS We reviewed F-FDG PET/CT studies of all consecutive women with pelvic malignancies who underwent ovarian transposition between 2007 and 2013. Studies were grouped according to the time period over which they were carried out. Findings were categorized by location, size, appearance (solid/mixed/cystic), presence of surgical clips, ovarian F-FDG uptake (maximum standardized uptake value), and attenuation values on CT (Hounsfield units). Group time-period differences were assessed. RESULTS Seventy-nine F-FDG PET/CT studies were reviewed, 30 before and 49 after transposition. Time-period groups after transposition were up to 4 months (18 studies), 4.1-12 months (n=14), and more than 12 months (n=17). After transposition, ovaries were located mainly in the paracolic gutter (n=32) and subhepatic regions (n=18). Surgical clips were present in 67%. Both ovaries appeared more solid 1 year after surgery than preoperatively (13.7% before vs. 61.3% after surgery; P<0.001). Transient F-FDG-avidity was observed in 11 ovaries. Hounsfield unit values were higher within 4 months after surgery than preoperatively, reverting thereafter to preoperative values. CONCLUSION After ovarian transposition, nonanatomic location, loss of cysts formation in favor of solid appearance over time, and intermittent F-FDG uptake of functioning transposed ovaries might mimic metastatic lesions. Careful interpretation of F-FDG PET/CT findings is mandatory in women with pelvic malignancies who have undergone ovarian transposition.
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Affiliation(s)
- Tima Davidson
- Departments of Nuclear Medicine.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Orna Komisar
- Diagnostic Imaging.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Jacob Korach
- Gynecologic Oncology.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Shira Felder
- Radiation Oncology, Chaim Sheba Medical Center, Tel Hashomer.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Sara Apter
- Diagnostic Imaging.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
| | - Simona Ben-Haim
- Departments of Nuclear Medicine.,Institute of Nuclear Medicine, University College London and UCH Hospitals, London, UK
| | - Tamar Perri
- Gynecologic Oncology.,Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
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28
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Hasanzadeh M, Sahmani R, Solhi E, Mokhtarzadeh A, Shadjou N, Mahboob S. Ultrasensitive immunoassay of carcinoma antigen 125 in untreated human plasma samples using gold nanoparticles with flower like morphology: A new platform in early stage diagnosis of ovarian cancer and efficient management. Int J Biol Macromol 2018; 119:913-925. [PMID: 30081127 DOI: 10.1016/j.ijbiomac.2018.08.008] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2018] [Revised: 07/28/2018] [Accepted: 08/02/2018] [Indexed: 12/25/2022]
Abstract
Ovarian cancer, as one of the most life-threatening malignancies among women worldwide, is usually diagnosed at the late stage despite up regulation of molecular markers such as carcinoma antigen 125 (CA 125) at the early stages of the malignancy. CA 125 is the only tumor marker recommended for clinical use in the diagnosis and management of ovarian cancer. The potential role of CA-125 for the early detection of ovarian cancer is controversial and has not yet been adopted for widespread screening efforts in asymptomatic women. Therefore, early detection of CA 125 in human biofluids is highly demanded. In the present study, a novel method was proposed for the fabrication of electrochemical immunosensor based reduced graphene oxide (RGO). Cysteamine capped gold nanoparticle (Cys-AuNPs) were deposited over the surface of ERGO probe using electrophoretic deposition method. These Cys-AuNPs/ERGO probes provide the favorable sites to attach the monoclonal antibody specific to CA 125 antigen. Cyclic voltammetry (CV), and square wave voltammetry (SWV) were applied for the electrochemical recognition of the biolayer. The represented signals demonstrates excellent figure of merits and good capability of the engineered immunosensor towards sensitive detection of CA 125. Quantitative measurements of CA 125 in human plasma samples have been demonstrated, showing the potential of the practical application of this novel immunosensor for the analysis of this biomarker in blood serum samples. This immunosensor has the ability of direct electron transfer as compared to earlier reported electrochemical immunosensors based electrochemical methods. Further, this immunosensor provides a very suitable and convenient alternative to replace the expensive commercially available methods such as immunohistochemistry. The following regression equation between the electrochemical current response and the CA 125 concentration range from 0.1 to 400 U/mL was found. The low limit of quantification for this immunosensor was 0.1 U/mL. To the best of our knowledge, this is the first reported on the direct immobilization of antibody on the surface of Cys-AuNPs/ERGO for fabrication of immunosensors.
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Affiliation(s)
- Mohammad Hasanzadeh
- Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
| | - Rahimeh Sahmani
- Department of Biochemistry, Higher Education Institute of Rab-Rashid, Tabriz, Iran
| | - Elham Solhi
- Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ahad Mokhtarzadeh
- Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Nasrin Shadjou
- Department of Nanochemistry, Nano Technology Research Center, Uremia University, Uremia 57154, Iran
| | - Soltanali Mahboob
- Department of Biochemistry, Higher Education Institute of Rab-Rashid, Tabriz, Iran
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29
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The Diagnostic Value of Serum CEA, CA-125, and ROMA Index in Low-Grade Serous Ovarian Cancer. INTERNATIONAL JOURNAL OF CANCER MANAGEMENT 2018. [DOI: 10.5812/ijcm.63397] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
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30
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Han C, Bellone S, Siegel ER, Altwerger G, Menderes G, Bonazzoli E, Egawa-Takata T, Pettinella F, Bianchi A, Riccio F, Zammataro L, Yadav G, Marto JA, Penet MF, Levine DA, Drapkin R, Patel A, Litkouhi B, Ratner E, Silasi DA, Huang GS, Azodi M, Schwartz PE, Santin AD. A novel multiple biomarker panel for the early detection of high-grade serous ovarian carcinoma. Gynecol Oncol 2018; 149:585-591. [PMID: 29572027 DOI: 10.1016/j.ygyno.2018.03.050] [Citation(s) in RCA: 52] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Revised: 03/13/2018] [Accepted: 03/15/2018] [Indexed: 12/18/2022]
Abstract
INTRODUCTION Since the majority of patients are diagnosed at an advanced stage, ovarian cancer remains the most lethal gynecologic malignancy. There is no single biomarker with the sensitivity and specificity required for effective cancer screening; therefore, we investigated a panel of novel biomarkers for the early detection of high-grade serous ovarian carcinoma. METHODS Twelve serum biomarkers with high differential gene expression and validated antibodies were selected: IL-1Ra, IL-6, Dkk-1, uPA, E-CAD, ErbB2, SLPI, HE4, CA125, LCN2, MSLN, and OPN. They were tested using Simple Plex™, a multi-analyte immunoassay platform, in samples collected from 172 patients who were either healthy, had benign gynecologic pathologies, or had high-grade serous ovarian adenocarcinomas. The receiver operating characteristic (ROC) curve, ROC area under the curve (AUC), and standard error (SE) of the AUC were obtained. Univariate ROC analyses and multivariate ROC analyses with the combination of multiple biomarkers were performed. RESULTS The 4-marker panel consisting of CA125, HE4, E-CAD, and IL-6 had the highest ROC AUC. When evaluated for the ability to distinguish early stage ovarian cancer from a non-cancer control, not only did this 4-marker panel (AUC=0.961) performed better than CA 125 alone (AUC=0.851; P=0.0150) and HE4 alone (AUC=0.870; P=0.0220), but also performed significantly better than the 2- marker combination of CA125+HE4 (AUC=0.922; P=0.0278). The 4-marker panel had the highest average sensitivity under the region of its ROC curve corresponding to specificity ranging from 100% down to ~95%. CONCLUSION The four-marker panel, CA125, HE4, E-CAD, and IL-6, shows potential in detecting serous ovarian cancer at earlier stages. Additional validation studies using the biomarker combination in ovarian cancer patients are warranted.
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Affiliation(s)
- Chanhee Han
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Stefania Bellone
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Eric R Siegel
- Department of Biostatistics, University of Arkansas for Medical Science, Little Rock, AR 72205, USA
| | - Gary Altwerger
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Gulden Menderes
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Elena Bonazzoli
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Tomomi Egawa-Takata
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Francesca Pettinella
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Anna Bianchi
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Francesco Riccio
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Luca Zammataro
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Ghanshyam Yadav
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Jarrod A Marto
- Department of Cancer Biology, Department of Oncologic Pathology, Blais Proteomic Center, Dana-Farber Cancer Institute, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
| | - Marie-France Penet
- Division of Cancer Imaging Research, The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Douglas A Levine
- Division of Gynecologic Oncology, Laura and Isaac Perlmutter Cancer Center, NYU Langone Health, New York, NY 10016, USA
| | - Ronny Drapkin
- Department of Obstetrics and Gynecology, Penn Ovarian Cancer Research Center, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA
| | - Abhijit Patel
- Department of Therapeutic Radiology, Yale School of Medicine, New Haven, CT 06510, USA
| | - Babak Litkouhi
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Elena Ratner
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Dan-Arin Silasi
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Gloria S Huang
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Masoud Azodi
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Peter E Schwartz
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA
| | - Alessandro D Santin
- Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, New Haven, CT 06520, USA.
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31
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Mathieu KB, Bedi DG, Thrower SL, Qayyum A, Bast RC. Screening for ovarian cancer: imaging challenges and opportunities for improvement. ULTRASOUND IN OBSTETRICS & GYNECOLOGY : THE OFFICIAL JOURNAL OF THE INTERNATIONAL SOCIETY OF ULTRASOUND IN OBSTETRICS AND GYNECOLOGY 2018; 51. [PMID: 28639753 PMCID: PMC5788737 DOI: 10.1002/uog.17557] [Citation(s) in RCA: 59] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/14/2023]
Abstract
The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) recently reported a reduction in the average overall mortality among ovarian cancer patients screened with an annual sequential, multimodal strategy that tracked biomarker CA125 over time, where increasing serum CA125 levels prompted ultrasound. However, multiple cases were documented wherein serum CA125 levels were rising, but ultrasound screens were normal, thus delaying surgical intervention. A significant factor which could contribute to false negatives is that many aggressive ovarian cancers are believed to arise from epithelial cells on the fimbriae of the fallopian tubes, which are not readily imaged. Moreover, because only a fraction of metastatic tumors may reach a sonographically-detectable size before they metastasize, annual screening with ultrasound may fail to detect a large fraction of early-stage ovarian cancers. The ability to detect ovarian carcinomas before they metastasize is critical and future efforts towards improving screening should focus on identifying unique features specific to aggressive, early-stage tumors, as well as improving imaging sensitivity to allow for detection of tubal lesions. Implementation of a three-stage multimodal screening strategy in which a third modality is employed in cases where the first-line blood-based assay is positive and the second-line ultrasound exam is negative may also prove fruitful in detecting early-stage cases missed by ultrasound.
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Affiliation(s)
- K B Mathieu
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, 1881 East Road, Unit 1902, Houston, TX, 77054, USA
| | - D G Bedi
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - S L Thrower
- Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, 1881 East Road, Unit 1902, Houston, TX, 77054, USA
| | - A Qayyum
- Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - R C Bast
- Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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32
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Campbell S, Gentry-Maharaj A. The role of transvaginal ultrasound in screening for ovarian cancer. Climacteric 2018; 21:221-226. [PMID: 29490504 DOI: 10.1080/13697137.2018.1433656] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Ovarian cancer is a low-prevalence postmenopausal cancer with a high mortality rate and is the fifth most lethal cancer in women. The most common serous subtype with TP53 mutations spreads rapidly throughout the peritoneal cavity (stage III/IV) when 5-year survival is 10%. If diagnosed while confined to the ovary (stage I), the survival rate exceeds 90%. This is the rationale for screening. Annual transvaginal ultrasound (TVU) scans used as a primary screening modality or as a second-line test following primary screening with serum CA125 (multimodal) have been investigated in several trials. Only two large randomized controlled trials have provided mortality data. The US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial studied over 78 000 women (randomized to screening with either TVU or CA125, or control) over 6 years with 14 years follow-up and found no mortality benefit from screening and increased morbidity in the screened arm. The UK Collaborative Trial of Ovarian Cancer Screening studied over 202 000 women randomized to TVU, multimodal or control in a 1 : 1 : 2 ratio over 7-11 years with 11 years follow-up. CA125 was interpreted by the Risk of Ovarian Cancer algorithm which identifies a rise in the level rather than a fixed cut-off. There was a late reduction in mortality after 7 years in the screened arm (23% in the multimodal arm and 21% in the TVU arm), but the overall reduction was not significant. Further follow-up may reveal whether TVU has a primary or secondary role in ovarian cancer screening.
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Affiliation(s)
| | - A Gentry-Maharaj
- b Gynaecological Cancer Research Centre, Department of Women's Cancer, Institute for Women's Health , University College London , London , UK
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33
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Ding M, Pan J, Guo Z, Liu Q, Yang C, Mao L. SATB1 is a Novel Molecular Target for Cancer Therapy. Cancer Invest 2018; 36:28-36. [PMID: 29381393 DOI: 10.1080/07357907.2018.1423688] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Affiliation(s)
- Meng Ding
- Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou University, Xuzhou, China
- Department of Urinary Surgery, The Affiliated Hospital of University Medical College, Xuzhou, China
| | - Jun Pan
- Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou University, Xuzhou, China
- Department of Urinary Surgery, The Affiliated Hospital of University Medical College, Xuzhou, China
| | - Zhicheng Guo
- Department of Urinary Surgery, The Affiliated Hospital of University Medical College, Xuzhou, China
| | - Quhe Liu
- Department of Urinary Surgery, The Affiliated Hospital of University Medical College, Xuzhou, China
| | - Chunhua Yang
- Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou University, Xuzhou, China
| | - Lijun Mao
- Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou University, Xuzhou, China
- Department of Urinary Surgery, The Affiliated Hospital of University Medical College, Xuzhou, China
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Kim HJ, Sung SH, Kim CY, Bae MK, Cho MS, Kim YH, Kim SC, Ju W. 14-3-3ζ Overexpression is Associated with Poor Prognosis in Ovarian Cancer. Yonsei Med J 2018; 59:51-56. [PMID: 29214776 PMCID: PMC5725364 DOI: 10.3349/ymj.2018.59.1.51] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2017] [Revised: 09/13/2017] [Accepted: 09/26/2017] [Indexed: 01/05/2023] Open
Abstract
PURPOSE 14-3-3ζregulates cell signaling, cell cycle progression, and apoptosis, and its overexpression is associated with disease recurrence and poor clinical outcomes in some solid tumors. However, its clinicopathological role in ovarian cancer is unknown. Our goal was to investigate whether 14-3-3ζis associated with ovarian cancer prognosis. MATERIALS AND METHODS We examined 14-3-3ζexpression by immunohistochemistry in ovarian cancer tissues obtained from 88 ovarian cancer patients. The examined tissues were of various histologies and stages. 14-3-3ζexpression was also analyzed by western blot in seven ovarian cancer cell lines and a primary ovary epithelial cell line. Cell viability was measured using an MTS-based assay following cisplatin treatment. RESULTS Among the ovarian cancer samples, 53.4% (47/88) showed high 14-3-3ζexpression, and 14-3-3ζoverexpression was positively correlated with more advanced pathologic stages and grades. 14-3-3ζoverexpression was also significantly associated with poor disease-free survival (DFS) and overall survival (OS) of ovarian cancer patients. Median DFS and OS were 1088 and 3905 days, respectively, in the high 14-3-3ζexpression group, but not reached in the low 14-3-3ζexpression group (p=0.004 and p=0.033, log-rank test, respectively). Downregulating 14-3-3ζby RNA interference in ovarian cancer cells led to enhanced sensitivity to cisplatin-induced cell death. CONCLUSION 14-3-3ζoverexpression might be a potential prognostic biomarker for ovarian cancer, and the inhibition of 14-3-3ζcould be a therapeutic option that enhances the antitumor activity of cisplatin.
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Affiliation(s)
- Hyun Jung Kim
- Department of Obstetrics and Gynecology, School of Medicine, Ewha Womans University, Seoul, Korea
- Innovative Research Center for Control and Prevention of Women's Cancer, Ewha Womans University Mokdong Hospital, Seoul, Korea
| | - Sun Hee Sung
- Department of Pathology, School of Medicine, Ewha Womans University, Seoul, Korea
| | - Chan Young Kim
- Department of Obstetrics and Gynecology, School of Medicine, Ewha Womans University, Seoul, Korea
- Innovative Research Center for Control and Prevention of Women's Cancer, Ewha Womans University Mokdong Hospital, Seoul, Korea
| | - Moon Kyoung Bae
- Department of Obstetrics and Gynecology, School of Medicine, Ewha Womans University, Seoul, Korea
- Innovative Research Center for Control and Prevention of Women's Cancer, Ewha Womans University Mokdong Hospital, Seoul, Korea
| | - Min Sun Cho
- Department of Pathology, School of Medicine, Ewha Womans University, Seoul, Korea
| | - Yun Hwan Kim
- Department of Obstetrics and Gynecology, School of Medicine, Ewha Womans University, Seoul, Korea
- Innovative Research Center for Control and Prevention of Women's Cancer, Ewha Womans University Mokdong Hospital, Seoul, Korea
| | - Seung Cheol Kim
- Department of Obstetrics and Gynecology, School of Medicine, Ewha Womans University, Seoul, Korea
- Innovative Research Center for Control and Prevention of Women's Cancer, Ewha Womans University Mokdong Hospital, Seoul, Korea
| | - Woong Ju
- Department of Obstetrics and Gynecology, School of Medicine, Ewha Womans University, Seoul, Korea
- Innovative Research Center for Control and Prevention of Women's Cancer, Ewha Womans University Mokdong Hospital, Seoul, Korea.
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35
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Stewart SL, Harewood R, Matz M, Rim SH, Sabatino SA, Ward KC, Weir HK. Disparities in ovarian cancer survival in the United States (2001-2009): Findings from the CONCORD-2 study. Cancer 2017; 123 Suppl 24:5138-5159. [PMID: 29205312 DOI: 10.1002/cncr.31027] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Revised: 08/10/2017] [Accepted: 08/25/2017] [Indexed: 12/31/2022]
Abstract
BACKGROUND Ovarian cancer is the fifth leading cause of cancer death among women in the United States. This study reports ovarian cancer survival by state, race, and stage at diagnosis using data from the CONCORD-2 study, the largest and most geographically comprehensive, population-based survival study to date. METHODS Data from women diagnosed with ovarian cancer between 2001 and 2009 from 37 states, covering 80% of the US population, were used in all analyses. Survival was estimated up to 5 years and was age standardized and adjusted for background mortality (net survival) using state-specific and race-specific life tables. RESULTS Among the 172,849 ovarian cancers diagnosed between 2001 and 2009, more than one-half were diagnosed at distant stage. Five-year net survival was 39.6% between 2001 and 2003 and 41% between 2004 and 2009. Black women had consistently worse survival compared with white women (29.6% from 2001-2003 and 31.1% from 2004-2009), despite similar stage distributions. Stage-specific survival for all races combined between 2004 and 2009 was 86.4% for localized stage, 60.9% for regional stage, and 27.4% for distant stage. CONCLUSIONS The current data demonstrate a large and persistent disparity in ovarian cancer survival among black women compared with white women in most states. Clinical and public health efforts that ensure all women who are diagnosed with ovarian cancer receive appropriate, guidelines-based treatment may help to decrease these disparities. Future research that focuses on the development of new methods or modalities to detect ovarian cancer at early stages, when survival is relatively high, will likely improve overall US ovarian cancer survival. Cancer 2017;123:5138-59. Published 2017. This article is a U.S. Government work and is in the public domain in the USA.
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Affiliation(s)
- Sherri L Stewart
- Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Rhea Harewood
- Cancer Survival Group, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Melissa Matz
- Cancer Survival Group, Department of Non-Communicable Disease Epidemiology, London School of Hygiene and Tropical Medicine, London, United Kingdom
| | - Sun Hee Rim
- Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Susan A Sabatino
- Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia
| | - Kevin C Ward
- Rollins School of Public Health, Emory University, Atlanta, Georgia
| | - Hannah K Weir
- Division of Cancer Prevention and Control, Centers for Disease Control and Prevention, Atlanta, Georgia
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Abramowicz JS, Timmerman D. Ovarian mass-differentiating benign from malignant: the value of the International Ovarian Tumor Analysis ultrasound rules. Am J Obstet Gynecol 2017; 217:652-660. [PMID: 28735703 DOI: 10.1016/j.ajog.2017.07.019] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2017] [Revised: 07/10/2017] [Accepted: 07/15/2017] [Indexed: 12/16/2022]
Abstract
Ovarian cancer, the fifth most common cause of cancer death among women, has the highest mortality rate of all gynecologic cancers. General survival rate is <50% but can reach 90% if disease is detected early. Ultrasound is presently the best modality to differentiate between benign and malignant status. The patient with a malignant mass should be referred to an oncology surgeon since results have been shown to be superior to treatment by a specialist. Several ultrasound-based scoring systems exist for assessing the risk of an ovarian tumor to be malignant. The International Ovarian Tumor Analysis group published 2 such systems: the ultrasound Simple Rules and the Assessment of Different NEoplasias in the adneXa model. The Simple Rules classifies a tumor as benign, malignant, or indeterminate and the Assessment of Different NEoplasias in the adneXa model determines the risk for a tumor to be benign or malignant and, if malignant, the risk of various stages. Sensitivity of the Simple Rules and Assessment of Different NEoplasias in the adneXa model (using a cut-off of 10% to predict malignancy) are 92% and 96.5%, respectively, and specificities are 96% and 71.3%, respectively. These models are the best predictive tests for the preoperative classification of adnexal tumors. Their intent is to help the specialist make management decisions when faced with a patient with a persistent ovarian mass. The models are simple, are easy to use, and have been validated in multiple reports but not in the United States. We suggest they should be validated and widely introduced into medical practice in the United States.
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Piszczek C, Ma J, Gould CH, Tseng P. Cancer Risk-Reducing Opportunities in Gynecologic Surgery. J Minim Invasive Gynecol 2017; 25:1179-1193. [PMID: 29097232 DOI: 10.1016/j.jmig.2017.10.025] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2017] [Revised: 10/20/2017] [Accepted: 10/21/2017] [Indexed: 12/16/2022]
Abstract
This review article discusses cancer risk-reducing opportunities in gynecologic surgery. We cover strategies to reduce ovarian and uterine cancer risk by presenting general practice guidelines and expanding on the literature behind clinical decision points. We address populations of women at increased hereditary risk and those at population risk. We specifically discuss risk-reducing salpingo-oophorectomy, prophylactic salpingectomy with delayed oophorectomy, concomitant hysterectomy, opportunistic salpingectomy, bilateral tubal ligation, and hysterectomy. For clinical scenarios in which data are limited or conflicting, we detail the studies on which clinicians' decisions hinge to allow the reader to weigh the available evidence.
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Affiliation(s)
- Carolyn Piszczek
- Division of Women's Services, Legacy Health System, Portland, Oregon.
| | - Jun Ma
- Divisions of Gynecologic Oncology, Legacy Medical Group, Portland, Oregon
| | - Claire H Gould
- Advanced Gynecology, Legacy Medical Group, Portland, Oregon
| | - Paul Tseng
- Divisions of Gynecologic Oncology, Legacy Medical Group, Portland, Oregon
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38
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Pandharipande PV, Lowry KP, Reinhold C, Atri M, Benson CB, Bhosale PR, Green ED, Kang SK, Lakhman Y, Maturen KE, Nicola R, Salazar GM, Shipp TD, Simpson L, Sussman BL, Uyeda J, Wall DJ, Whitcomb B, Zelop CM, Glanc P. ACR Appropriateness Criteria ® Ovarian Cancer Screening. J Am Coll Radiol 2017; 14:S490-S499. [DOI: 10.1016/j.jacr.2017.08.049] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2017] [Accepted: 08/23/2017] [Indexed: 11/27/2022]
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Ring KL, Garcia C, Thomas MH, Modesitt SC. Current and future role of genetic screening in gynecologic malignancies. Am J Obstet Gynecol 2017; 217:512-521. [PMID: 28411145 DOI: 10.1016/j.ajog.2017.04.011] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2016] [Revised: 03/28/2017] [Accepted: 04/04/2017] [Indexed: 02/06/2023]
Abstract
The world of hereditary cancers has seen exponential growth in recent years. While hereditary breast and ovarian cancer and Lynch syndrome account for the majority of mutations encountered by gynecologists, newly identified deleterious genetic mutations continue to be unearthed with their associated risks of malignancies. However, these advances in genetic cancer predispositions then force practitioners and their patients to confront the uncertainties of these less commonly identified mutations and the fact that there is limited evidence to guide them in expected cancer risk and appropriate risk-reduction strategies. Given the speed of information, it is imperative to involve cancer genetics experts when counseling these patients. In addition, coordination of screening and care in conjunction with specialty high-risk clinics, if available, allows for patients to have centralized management for multiple cancer risks under the guidance of physicians with experience counseling these patients. The objective of this review is to present the current literature regarding genetic mutations associated with gynecologic malignancies as well to propose screening and risk-reduction options for these high-risk patients.
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40
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Gesi C, Carmassi C, Sancassiani F, Gadducci A, Dell'Osso L. Post-traumatic Stress Disorder in patients with ovarian cancer. Int Rev Psychiatry 2017; 29:403-408. [PMID: 28681619 DOI: 10.1080/09540261.2017.1307168] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/25/2023]
Abstract
Ovarian cancer (OC) is one of the deadliest malignancies. The impact of this diagnosis is, therefore, highly traumatic, and affected women are prone to significant distress during the whole course of the disease. The present paper is aimed to review extant literature about the relationship between OC and Post-traumatic Stress Disorder (PTSD).
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Affiliation(s)
- Camilla Gesi
- a Department of Clinical and Experimental Medicine , University of Pisa , Pisa , Italy
| | - Claudia Carmassi
- a Department of Clinical and Experimental Medicine , University of Pisa , Pisa , Italy
| | - Federica Sancassiani
- b Department of Medical Sciences and Public Health , University of Cagliari , Cagliari , Italy
| | - Angiolo Gadducci
- a Department of Clinical and Experimental Medicine , University of Pisa , Pisa , Italy
| | - Liliana Dell'Osso
- a Department of Clinical and Experimental Medicine , University of Pisa , Pisa , Italy
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Committee Opinion No. 716: The Role of the Obstetrician-Gynecologist in the Early Detection of Epithelial Ovarian Cancer in Women at Average Risk. Obstet Gynecol 2017; 130:e146-e149. [PMID: 28832487 DOI: 10.1097/aog.0000000000002299] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Ovarian cancer is the second most common type of female reproductive cancer, and more women die from ovarian cancer than from cervical cancer and uterine cancer combined. Currently, there is no strategy for early detection of ovarian cancer that reduces ovarian cancer mortality. Taking a detailed personal and family history for breast, gynecologic, and colon cancer facilitates categorizing women based on their risk (average risk or high risk) of developing epithelial ovarian cancer. Women with a strong family history of ovarian, breast, or colon cancer may have hereditary breast and ovarian cancer syndrome (BRCA mutation) or hereditary nonpolyposis colorectal cancer (Lynch syndrome), and these women are at increased risk of developing ovarian cancer. Women with these conditions should be referred for formal genetic counseling to better assess their cancer risk, including their risk of ovarian cancer. If appropriate, these women may be offered additional testing for early detection of ovarian cancer. The use of transvaginal ultrasonography and tumor markers (such as cancer antigen 125), alone or in combination, for the early detection of ovarian cancer in average-risk women have not been proved to reduce mortality, and harms exist from invasive diagnostic testing (eg, surgery) resulting from false-positive test results. The patient and her obstetrician-gynecologist should maintain an appropriate level of suspicion when potentially relevant signs and symptoms of ovarian cancer are present.
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Molecular Alterations of TP53 are a Defining Feature of Ovarian High-Grade Serous Carcinoma: A Rereview of Cases Lacking TP53 Mutations in The Cancer Genome Atlas Ovarian Study. Int J Gynecol Pathol 2017; 35:48-55. [PMID: 26166714 DOI: 10.1097/pgp.0000000000000207] [Citation(s) in RCA: 121] [Impact Index Per Article: 15.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
The Cancer Genome Atlas has reported that 96% of ovarian high-grade serous carcinomas (HGSCs) have TP53 somatic mutations suggesting that mutation of this gene is a defining feature of this neoplasm. In the current study, 5 gynecologic pathologists independently evaluated hematoxylin and eosin slides of 14 available cases from The Cancer Genome Atlas classified as HGSC that lacked a TP53 mutation. The histologic diagnoses rendered by these pathologists and the accompanying molecular genetic data are the subject of this report. Only 1 case (Case 5), which contained a homozygous deletion of TP53, had unanimous interobserver agreement for a diagnosis of pure HGSC. In 1 case (Case 3), all 5 observers (100%) rendered a diagnosis of HGSC; however, 3 observers (60%) noted that the histologic features were not classic for HGSC and suggested this case may have arisen from a low-grade serous carcinoma (arisen from an alternate pathway compared with the usual HGSC). In 2 cases (Cases 4 and 12), only 3 observers (60%) in each case, respectively, interpreted it as having a component of HGSC. In the remaining 10 (71%) of tumors (Cases 1, 2, 6-11, 13, and 14), the consensus diagnosis was not HGSC, with individual diagnoses including low-grade serous carcinoma, high-grade endometrioid carcinoma, HGSC, metastatic carcinoma, clear cell carcinoma, atypical proliferative (borderline) serous tumor, and adenocarcinoma, not otherwise specified. Therefore, 13 (93%) of the tumors (Cases 1-4 and 6-14) were either not a pure HGSC or represented a diagnosis other than HGSC, all with molecular results not characteristic of HGSC. Accordingly, our review of the TP53 wild-type HGSCs reported in The Cancer Genome Atlas suggests that 100% of de novo HGSCs contain TP53 somatic mutations or deletions, with the exception of the rare HGSCs that develop from a low-grade serous tumor precursor. We, therefore, propose that lack of molecular alterations of TP53 are essentially inconsistent with the diagnosis of ovarian HGSC and that tumors diagnosed as such should be rigorously reassessed to achieve correct classification.
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Buhling KJ, Lezon S, Eulenburg C, Schmalfeldt B. The role of transvaginal ultrasonography for detecting ovarian cancer in an asymptomatic screening population: a systematic review. Arch Gynecol Obstet 2017; 295:1259-1268. [DOI: 10.1007/s00404-017-4346-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Accepted: 03/09/2017] [Indexed: 11/30/2022]
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Scheib SA. A Laparoendoscopic Single-site Surgical Approach to Laparoscopic Salpingectomy. J Minim Invasive Gynecol 2017; 25:326-327. [PMID: 28342812 DOI: 10.1016/j.jmig.2017.03.013] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2016] [Revised: 03/06/2017] [Accepted: 03/15/2017] [Indexed: 11/18/2022]
Abstract
STUDY OBJECTIVE To demonstrate a laparoendoscopic single-site (LESS) surgical approach to salpingectomy. DESIGN A technical video showing step-by-step a LESS surgical approach to salpingectomy (Canadian Task Force classification level III). Institutional review board approval was not required for this study. SETTING Of all gynecologic cancer types, ovarian cancer has the highest mortality rate and is the fifth leading cause of cancer deaths among women [1,2]. The leading theory of epithelial ovarian carcinogenesis indicates that serous, endometrioid, and clear cell ovarian carcinomas originated from the fallopian tube and endometrium and not directly from the ovary itself [1-10]. This has led to the use of prophylactic salpingectomy as a theoretical form of ovarian cancer risk reduction at the time of hysterectomy or as a means of tubal sterilization. Prophylactic salpingectomy does not appear to increase the risk of complications and appears to be safe [2]. Ovarian function does not seem to be compromised by salpingectomy based on serum markers or response rates with in vitro fertilization [11-16]. A LESS approach may reduce the morbidity associated with the placement of multiple ports and can improve cosmetic outcomes. Prophylactic LESS bilateral salpingo-oohorectomy was shown to be feasible and safe for high-risk patients for ovarian cancer [17]. INTERVENTIONS Laparoscopic salpingectomy at the time of hysterectomy or as a means of tubal sterilization using the LESS technique. CONCLUSION This is a simple and reproducible technique for preventing major complications associated with LESS salpingectomy. This approach permits easier specimen retrieval because of the large solitary incision that is made. There is a significant improvement in cosmetic satisfaction when compared with a traditional laparoscopic approach in the setting of prophylactic risk reduction surgery [18].
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Affiliation(s)
- Stacey A Scheib
- Division of Gynecologic Specialties, Department of Gynecology and Obstetrics, Johns Hopkins University Hospital, Baltimore, Maryland.
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45
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Baldwin LA, Pavlik EJ, Ueland E, Brown HE, Ladd KM, Huang B, DeSimone CP, van Nagell JR, Ueland FR, Miller RW. Complications from Surgeries Related to Ovarian Cancer Screening. Diagnostics (Basel) 2017; 7:diagnostics7010016. [PMID: 28282907 PMCID: PMC5373025 DOI: 10.3390/diagnostics7010016] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2016] [Revised: 02/24/2017] [Accepted: 02/28/2017] [Indexed: 01/07/2023] Open
Abstract
The aim of this study was to evaluate complications of surgical intervention for participants in the Kentucky Ovarian Cancer Screening Program and compare results to those of the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. A retrospective database review included 657 patients who underwent surgery for a positive screen in the Kentucky Ovarian Cancer Screening Program from 1988–2014. Data were abstracted from operative reports, discharge summaries, and office notes for 406 patients. Another 142 patients with incomplete records were interviewed by phone. Complete information was available for 548 patients. Complications were graded using the Clavien–Dindo (C–D) Classification of Surgical Complications and considered minor if assigned Grade I (any deviation from normal course, minor medications) or Grade II (other pharmacological treatment, blood transfusion). C–D Grade III complications (those requiring surgical, endoscopic, or radiologic intervention) and C–D Grade IV complications (those which are life threatening) were considered “major”. Statistical analysis was performed using SAS 9.4 software. Complications were documented in 54/548 (10%) subjects. For women with malignancy, 17/90 (19%) had complications compared to 37/458 (8%) with benign pathology (p < 0.003). For non-cancer surgery, obesity was associated with increased complications (p = 0.0028). Fifty patients had minor complications classified as C–D Grade II or less. Three of 4 patients with Grade IV complications had malignancy (p < 0.0004). In the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial, 212 women had surgery for ovarian malignancy, and 95 had at least one complication (45%). Of the 1080 women with non-cancer surgery, 163 had at least one complication (15%). Compared to the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial, the Kentucky Ovarian Cancer Screening Program had significantly fewer complications from both cancer and non-cancer surgery (p < 0.0001 and p = 0.002, respectively). Complications resulting from surgery performed as a result of the Kentucky Ovarian Cancer Screening Program were infrequent and significantly fewer than reported in the Prostate, Lung, Colorectal and Ovarian Cancer Screening trial. Complications were mostly minor (93%) and were more common in cancer versus non-cancer surgery.
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Affiliation(s)
- Lauren A Baldwin
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center and the Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0293, USA.
| | - Edward J Pavlik
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center and the Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0293, USA.
| | - Emma Ueland
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center and the Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0293, USA.
| | - Hannah E Brown
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center and the Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0293, USA.
| | - Kelsey M Ladd
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center and the Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0293, USA.
| | - Bin Huang
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center and the Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0293, USA.
| | - Christopher P DeSimone
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center and the Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0293, USA.
| | - John R van Nagell
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center and the Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0293, USA.
| | - Frederick R Ueland
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center and the Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0293, USA.
| | - Rachel W Miller
- Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, The University of Kentucky Chandler Medical Center and the Markey Cancer Center, 800 Rose Street, Lexington, KY 40536-0293, USA.
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46
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Basu P, Vale D. Screening for Epithelial Ovarian Cancer: An Updated Review. INDIAN JOURNAL OF GYNECOLOGIC ONCOLOGY 2017. [DOI: 10.1007/s40944-017-0100-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
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47
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Sundaram KM, Zhang Y, Mitra AK, Kouadio JLK, Gwin K, Kossiakoff AA, Roman BB, Lengyel E, Piccirilli JA. Prolactin Receptor-Mediated Internalization of Imaging Agents Detects Epithelial Ovarian Cancer with Enhanced Sensitivity and Specificity. Cancer Res 2017; 77:1684-1696. [PMID: 28202518 DOI: 10.1158/0008-5472.can-16-1454] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Revised: 12/02/2016] [Accepted: 12/21/2016] [Indexed: 01/24/2023]
Abstract
Poor prognosis of ovarian cancer, the deadliest of the gynecologic malignancies, reflects major limitations associated with detection and diagnosis. Current methods lack high sensitivity to detect small tumors and high specificity to distinguish malignant from benign tissue, both impeding diagnosis of early and metastatic cancer stages and leading to costly and invasive surgeries. Tissue microarray analysis revealed that >98% of ovarian cancers express the prolactin receptor (PRLR), forming the basis of a new molecular imaging strategy. We fused human placental lactogen (hPL), a specific and tight binding PRLR ligand, to magnetic resonance imaging (gadolinium) and near-infrared fluorescence imaging agents. Both in tissue culture and in mouse models, these imaging bioconjugates underwent selective internalization into ovarian cancer cells via PRLR-mediated endocytosis. Compared with current clinical MRI techniques, this targeted approach yielded both enhanced signal-to-noise ratio from accumulation of signal via selective internalization and improved specificity conferred by PRLR upregulation in malignant ovarian cancer. These features endow PRLR-targeted imaging with the potential to transform ovarian cancer detection. Cancer Res; 77(7); 1684-96. ©2017 AACR.
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Affiliation(s)
- Karthik M Sundaram
- Department of Biochemistry & Molecular Biology, and Chemistry, The University of Chicago, Chicago, Illinois
| | - Yilin Zhang
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, Chicago, Illinois
| | - Anirban K Mitra
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, Chicago, Illinois
| | - Jean-Louis K Kouadio
- Department of Biochemistry & Molecular Biology, and Chemistry, The University of Chicago, Chicago, Illinois
| | - Katja Gwin
- Department of Pathology, The University of Chicago, Chicago, Illinois
| | - Anthony A Kossiakoff
- Department of Biochemistry & Molecular Biology, and Chemistry, The University of Chicago, Chicago, Illinois
| | - Brian B Roman
- Department of Radiology, The University of Chicago, Chicago, Illinois
| | - Ernst Lengyel
- Department of Obstetrics and Gynecology/Section of Gynecologic Oncology, The University of Chicago, Chicago, Illinois.
| | - Joseph A Piccirilli
- Department of Biochemistry & Molecular Biology, and Chemistry, The University of Chicago, Chicago, Illinois.
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48
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Mo Q, Zhang Y, Jin X, Gao Y, Wu Y, Hao X, Gao Q, Chen P. Geldanamycin, an inhibitor of Hsp90, increases paclitaxel-mediated toxicity in ovarian cancer cells through sustained activation of the p38/H2AX axis. Tumour Biol 2016; 37:14745-14755. [PMID: 27629142 DOI: 10.1007/s13277-016-5297-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2016] [Accepted: 08/31/2016] [Indexed: 12/18/2022] Open
Abstract
Paclitaxel is a mitotic inhibitor used in ovarian cancer chemotherapy. Unfortunately, due to the rapid genetic and epigenetic changes in adaptation to stress induced by anticancer drugs, cancer cells are often able to become resistant to single or multiple anticancer agents. However, it remains largely unknown how paclitaxel resistance happens. In this study, we generated a cell line of acquired resistance to paclitaxel therapy, A2780T, which is cross-resistant to other antimitotic drugs, such as PLK1 inhibitor or AURKA inhibitor. Immunoblotting revealed significant alterations in cell-cycle-related and apoptotic-related proteins involved in key signaling pathways. In particular, phosphorylation of p38, which activates H2AX, was significantly decreased in A2780T cells compared to the parental A2780 cells. Geldanamycin (GA), an inhibitor of Hsp90, sustained activation of the p38/H2AX axis, and A2780T cells were shown to be more sensitive to GA compared to A2780 cells. Furthermore, treatment of A2780 and A2780T cells with GA significantly enhanced sensitivity to paclitaxel. Meanwhile, GA cooperated with paclitaxel to suppress tumor growth in a mouse ovarian cancer xenograft model. In conclusion, GA may sensitize a subset of ovarian cancer to paclitaxel, particularly those tumors in which resistance is driven by inactivation of p38/H2AX axis.
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Affiliation(s)
- Qingqing Mo
- Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Yu Zhang
- Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Xin Jin
- Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Yue Gao
- Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Yuan Wu
- Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Xing Hao
- Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China
| | - Qinglei Gao
- Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
| | - Pingbo Chen
- Cancer Biology Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, China.
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Prediction of Epithelial Ovarian Cancer in Low Resource-Setting Countries: Single or Combined Biomarkers? INDIAN JOURNAL OF GYNECOLOGIC ONCOLOGY 2016. [DOI: 10.1007/s40944-016-0075-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Giornelli GH. Management of relapsed ovarian cancer: a review. SPRINGERPLUS 2016; 5:1197. [PMID: 27516935 PMCID: PMC4963348 DOI: 10.1186/s40064-016-2660-0] [Citation(s) in RCA: 87] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/15/2016] [Accepted: 06/24/2016] [Indexed: 01/21/2023]
Abstract
Around 70 % of ovarian cancer patients relapse after primary cytoreductive surgery and standard first-line chemotherapy. The biology of relapse remains unclear, but cancer stem cells seem to play an important role. There are still some areas of controversy on how to manage these relapses and or progressions that occur almost unavoidably in the course of this disease with shorter intervals between them as the natural history of this disease develops. The goal of treatments investigated in this neoplasm has shifted to maintenance therapy, trying to extend the progression free intervals in a disease that is becoming more and more protracted.
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Affiliation(s)
- Gonzalo H Giornelli
- Genital-Urinary Department, Instituto Alexander Fleming, Cramer 1180, C1426ANZ Buenos Aires, Argentina
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