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Aliabadi AR, Wilailak S, McNally O, Berek JS, Sridhar A. Contraceptive strategies for reducing the risk of reproductive cancers. Int J Gynaecol Obstet 2024; 166:141-151. [PMID: 38725288 DOI: 10.1002/ijgo.15567] [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: 06/27/2024]
Abstract
Reproductive cancers, encompassing various malignancies like endometrial, ovarian, cervical cancer, and gestational trophoblastic neoplasia, pose a significant global health burden. Understanding their patterns is vital for effective prevention and management. Contraceptives show a protective effect against some of these cancers. This clinical guidance document aims to elucidate the disease burden of reproductive cancers and the evidence supporting contraceptive methods in prevention and management. Regional disparities in incidence and mortality highlight the urgent need for targeted interventions, particularly in low-resource settings. Healthcare providers must weigh individual risk profiles and medical eligibility criteria when discussing contraceptive options. Enhanced health literacy through direct patient education is essential for leveraging low-cost behavioral interventions to mitigate reproductive cancer risks.
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Affiliation(s)
- A R Aliabadi
- Department of Obstetrics, Gynecology and Reproductive Sciences, The University of California, San Francisco, San Francisco, California, USA
- Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA
| | - Sarikapan Wilailak
- Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand
| | - Orla McNally
- Department of Oncology and Dysplasia, The Royal Women's Hospital, Melbourne, Victoria, Australia
| | - Jonathan S Berek
- Stanford Cancer Institute, Stanford University School of Medicine, Stanford, California, USA
| | - Aparna Sridhar
- Department of Obstetrics and Gynecology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA
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Hotton J, Gauchotte G, Mougel R, Migliorini M, Lacomme S, Battaglia-Hsu SF, Agopiantz M. Expressions of HuR, Methyl-HuR and Phospho-HuR in Endometrial Endometrioid Adenocarcinoma Are Associated with Clinical Features. Int J Mol Sci 2024; 25:954. [PMID: 38256026 PMCID: PMC10815350 DOI: 10.3390/ijms25020954] [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: 12/14/2023] [Revised: 01/03/2024] [Accepted: 01/09/2024] [Indexed: 01/24/2024] Open
Abstract
HuR regulates cytoplasmic mRNA stability and translatability, with its expression correlating with adverse outcomes in various cancers. This study aimed to assess the prognostic value and pro-oncogenic properties of HuR and its post-translational isoforms methyl-HuR and phospho-HuR in endometrial adenocarcinoma. Examining 89 endometrioid adenocarcinomas, we analyzed the relationship between HuR nuclear or cytoplasmic immunostaining, tumor-cell proliferation, and patient survival. HuR cytoplasmic expression was significantly increased in grade 3 vs. grade 1 adenocarcinomas (p < 0.001), correlating with worse overall survival (OS) (p = 0.02). Methyl-HuR cytoplasmic expression significantly decreased in grade 3 vs. grade 1 adenocarcinomas (p < 0.001) and correlated with better OS (p = 0.002). Phospho-HuR nuclear expression significantly decreased in grade 3 vs. grade 1 adenocarcinomas (p < 0.001) and non-significantly correlated with increased OS (p = 0.06). Cytoplasmic HuR expression strongly correlated with proliferation markers MCM6 (rho = 0.59 and p < 0.001) and Ki67 (rho = 0.49 and p < 0.001). Conversely, these latter inversely correlated with cytoplasmic methyl-HuR and nuclear phospho-HuR. Cytoplasmic HuR expression is a poor prognosis marker in endometrioid endometrial adenocarcinoma, while cytoplasmic methyl-HuR and nuclear phosphoHuR expressions are markers of better prognosis. This study highlights HuR as a promising potential therapeutic target, especially in treatment-resistant tumors, though further research is needed to understand the mechanisms regulating HuR subcellular localization and post-translational modifications.
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Affiliation(s)
- Judicaël Hotton
- Department of Gynecology and Obstetrics, CHRU de Nancy, Université de Lorraine, 54000 Nancy, France;
- INSERM U1256 NGERE, Université de Lorraine, 54500 Vandœuvre-lès-Nancy, France; (G.G.); (R.M.); (M.M.); (S.-F.B.-H.)
| | - Guillaume Gauchotte
- INSERM U1256 NGERE, Université de Lorraine, 54500 Vandœuvre-lès-Nancy, France; (G.G.); (R.M.); (M.M.); (S.-F.B.-H.)
- Department of Biopathology CHRU of Nancy, Institut de Cancérologie de Lorraine, BBB, CHRU de Nancy, Université de Lorraine, 54511 Vandœuvre-lès-Nancy, France
- Centre de Ressources Biologiques, BB-0033-00035, CHRU de Nancy, 54000 Nancy, France;
| | - Romane Mougel
- INSERM U1256 NGERE, Université de Lorraine, 54500 Vandœuvre-lès-Nancy, France; (G.G.); (R.M.); (M.M.); (S.-F.B.-H.)
- Department of Reproductive Medicine, CHRU de Nancy, Université de Lorraine, 54000 Nancy, France
| | - Mégane Migliorini
- INSERM U1256 NGERE, Université de Lorraine, 54500 Vandœuvre-lès-Nancy, France; (G.G.); (R.M.); (M.M.); (S.-F.B.-H.)
| | - Stéphanie Lacomme
- Centre de Ressources Biologiques, BB-0033-00035, CHRU de Nancy, 54000 Nancy, France;
| | - Shyue-Fang Battaglia-Hsu
- INSERM U1256 NGERE, Université de Lorraine, 54500 Vandœuvre-lès-Nancy, France; (G.G.); (R.M.); (M.M.); (S.-F.B.-H.)
| | - Mikaël Agopiantz
- INSERM U1256 NGERE, Université de Lorraine, 54500 Vandœuvre-lès-Nancy, France; (G.G.); (R.M.); (M.M.); (S.-F.B.-H.)
- Department of Reproductive Medicine, CHRU de Nancy, Université de Lorraine, 54000 Nancy, France
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Pados G, Zouzoulas D, Tsolakidis D. Recent management of endometrial cancer: a narrative review of the literature. Front Med (Lausanne) 2024; 10:1244634. [PMID: 38235267 PMCID: PMC10792696 DOI: 10.3389/fmed.2023.1244634] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Accepted: 11/23/2023] [Indexed: 01/19/2024] Open
Abstract
Endometrial cancer is a common female gynecological neoplasia and its incidence rate has increased in the past years. Due to its predominant symptoms, most women will present uterine bleeding. It is usually diagnosed at an early stage and surgery has an important role in the treatment plan. The prognosis and quality of life of these patients can be quite favorable, if proper treatment is offered by surgeons. Traditionally, more invasive approaches and procedures were offered to these patients, but recent data suggest that more conservative and minimal invasive choices can be adopted in the treatment algorithm. Minimal invasive surgery, such as laparoscopy and robotic surgery, should be considered as an acceptable alternative, compared to laparotomy with less comorbidities and similar oncological and survival outcomes. Furthermore, sentinel lymph node biopsy has emerged in the surgical staging of endometrial cancer, in order to replace comprehensive lymphadenectomy. It is associated with less intra- and postoperative complications, while preliminary data show no difference in survival rates. However, sentinel lymph node biopsy should be offered within a strict algorithm, to avoid residual metastatic disease. The aim of this review is to analyze all the available data for the application of minimal invasive surgery in early endometrial cancer and especially the role of sentinel lymph node biopsy.
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Affiliation(s)
- George Pados
- Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, “Papageorgiou” Hospital, Thessaloniki, Greece
- Center for Endoscopic Surgery “Diavalkaniko” Hospital, Thessaloniki, Greece
| | - Dimitrios Zouzoulas
- Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, “Papageorgiou” Hospital, Thessaloniki, Greece
| | - Dimitrios Tsolakidis
- Department of Obstetrics & Gynecology, Aristotle University of Thessaloniki, “Papageorgiou” Hospital, Thessaloniki, Greece
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Olarewaju E, Obeng-Gyasi E. Cadmium, Lead, Chronic Physiological Stress and Endometrial Cancer: How Environmental Policy Can Alter the Exposure of At-Risk Women in the United States. Healthcare (Basel) 2023; 11:healthcare11091278. [PMID: 37174820 PMCID: PMC10178079 DOI: 10.3390/healthcare11091278] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 04/04/2023] [Accepted: 04/27/2023] [Indexed: 05/15/2023] Open
Abstract
The health and life outcomes of individuals are intertwined with the context in which they grow and live. The totality of exposures one experiences affects health in the short term and throughout the life course. Environmental exposure to multiple contaminants can increase stress levels in individuals and neighborhoods with psychosocial stressors such as crime, drug and alcohol misuse, and violence also taking a toll on individual and neighborhood wellbeing. In addition, the availability, organization, and quality of local institutions and infrastructure all affect health in the short and long term. The role of these factors in endometrial cancer will be explored in this paper. In addition, policy implications regarding lead, chronic physiological stress, and endometrial cancer will be explored to ascertain the impact of these factors on at-risk women.
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Affiliation(s)
- Elizabeth Olarewaju
- Department of Built Environment, North Carolina A&T State University, Greensboro, NC 27411, USA
- Environmental Health and Disease Laboratory, North Carolina A&T State University, Greensboro, NC 27411, USA
| | - Emmanuel Obeng-Gyasi
- Department of Built Environment, North Carolina A&T State University, Greensboro, NC 27411, USA
- Environmental Health and Disease Laboratory, North Carolina A&T State University, Greensboro, NC 27411, USA
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Wang J, Meng F, Mao F. Single cell sequencing analysis and transcriptome analysis constructed the liquid-liquid phase separation(LLPS)-related prognostic model for endometrial cancer. Front Oncol 2022; 12:1005472. [PMID: 36185238 PMCID: PMC9515536 DOI: 10.3389/fonc.2022.1005472] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Accepted: 08/18/2022] [Indexed: 11/13/2022] Open
Abstract
Background Endometrial cancer is one of the most common gynecological tumors in developed countries. Our understanding of the pathogenesis of endometrial cancer and the changes in the immune microenvironment are still unclear. It is necessary to explore new biomarkers to guide the diagnosis and treatment of endometrial cancer. Methods The GEO database was used to download the endometrial cancer single cell sequencing dataset GSE173682. The UCSC database was used to download transcriptome sequencing data. The validation set was the transcriptome dataset GSE119041, which was retrieved from the GEO database. On the DrLLPS website, liquid-liquid phase separation-related genes can be downloaded. Relevant hub genes were found using weighted co-expression network analysis and dimension reduction clustering analysis. Prognostic models were built using Lasso regression and univariate COX regression. Analyses of immune infiltration were employed to investigate the endometrial cancer immunological microenvironment. The expression of model genes in endometrial cancer was confirmed using a PCR test. Results We created an LLPS-related predictive model for endometrial cancer by extensive study, and it consists of four genes: EIF2S2, SNRPC, PRELID1, and NDUFB9. Patients with endometrial cancer may be classified into high-risk and low-risk groups based on their risk scores, and those in the high-risk group had significantly worse prognoses (P<0.05). Additionally, there were notable variations in the immunological milieu between the groups at high and low risk. EIF2S2, SNRPC, PRELID1, and NDUFB9 were all up-regulated in endometrial cancer tissues, according to PCR results. Conclusions Our study can provide a certain reference for the diagnosis and treatment of endometrial cancer.
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Affiliation(s)
- Jiayang Wang
- Department of Radiotherapy, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, China
| | - Fei Meng
- Department of Gynaecology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, China
| | - Fei Mao
- Department of Urology, The Affiliated Huaian No. 1 People’s Hospital of Nanjing Medical University, Huaian, China
- *Correspondence: Fei Mao,
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Mandato VD, Palicelli A, Torricelli F, Mastrofilippo V, Leone C, Dicarlo V, Tafuni A, Santandrea G, Annunziata G, Generali M, Pirillo D, Ciarlini G, Aguzzoli L. Should Endometrial Cancer Treatment Be Centralized? BIOLOGY 2022; 11:768. [PMID: 35625496 PMCID: PMC9138425 DOI: 10.3390/biology11050768] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Revised: 05/10/2022] [Accepted: 05/13/2022] [Indexed: 05/17/2023]
Abstract
Endometrial cancer (EC) is the most common malignancy of the female genital tract in Western and emerging countries. In 2012, new cancer cases numbered 319,605, and 76,160 cancer deaths were diagnosed worldwide. ECs are usually diagnosed after menopause; 70% of ECs are diagnosed at an early stage with a favorable prognosis and a 5-year overall survival rate of 77%. On the contrary, women with advanced or recurrent disease have extremely poor outcomes because they show a low response rate to conventional chemotherapy. EC is generally considered easy to treat, although it presents a 5-year mortality of 25%. Though the guidelines (GLs) recommend treatment in specialized centers by physicians specializing in gynecologic oncology, most women are managed by general gynecologists, resulting in differences and discrepancies in clinical management. In this paper we reviewed the literature with the aim of highlighting where the treatment of EC patients requires gynecologic oncologists, as suggested by the GLs. Moreover, we sought to identify the causes of the lack of GL adherence, suggesting useful changes to ensure adequate treatment for all EC patients.
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Affiliation(s)
- Vincenzo Dario Mandato
- Unit of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; (V.M.); (C.L.); (V.D.); (G.A.); (M.G.); (D.P.)
| | - Andrea Palicelli
- Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; (A.P.); (A.T.); (G.S.)
| | - Federica Torricelli
- Laboratory of Translational Research, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy;
| | - Valentina Mastrofilippo
- Unit of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; (V.M.); (C.L.); (V.D.); (G.A.); (M.G.); (D.P.)
| | - Chiara Leone
- Unit of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; (V.M.); (C.L.); (V.D.); (G.A.); (M.G.); (D.P.)
| | - Vittoria Dicarlo
- Unit of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; (V.M.); (C.L.); (V.D.); (G.A.); (M.G.); (D.P.)
| | - Alessandro Tafuni
- Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; (A.P.); (A.T.); (G.S.)
- Pathology Unit, Department of Medicine and Surgery, University of Parma, 43121 Parma, Italy
| | - Giacomo Santandrea
- Pathology Unit, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; (A.P.); (A.T.); (G.S.)
- Clinical and Experimental Medicine PhD Program, University of Modena and Reggio Emilia, 41121 Modena, Italy
| | - Gianluca Annunziata
- Unit of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; (V.M.); (C.L.); (V.D.); (G.A.); (M.G.); (D.P.)
| | - Matteo Generali
- Unit of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; (V.M.); (C.L.); (V.D.); (G.A.); (M.G.); (D.P.)
| | - Debora Pirillo
- Unit of Obstetrics and Gynecology, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; (V.M.); (C.L.); (V.D.); (G.A.); (M.G.); (D.P.)
| | - Gino Ciarlini
- Unit of Surgical Gynecol Oncology, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; (G.C.); (L.A.)
| | - Lorenzo Aguzzoli
- Unit of Surgical Gynecol Oncology, Azienda USL-IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; (G.C.); (L.A.)
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Telomere and Telomerase-Associated Proteins in Endometrial Carcinogenesis and Cancer-Associated Survival. Int J Mol Sci 2022; 23:ijms23020626. [PMID: 35054812 PMCID: PMC8775816 DOI: 10.3390/ijms23020626] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2021] [Revised: 12/29/2021] [Accepted: 12/31/2021] [Indexed: 12/30/2022] Open
Abstract
Risk of relapse of endometrial cancer (EC) after surgical treatment is 13% and recurrent disease carries a poor prognosis. Research into prognostic indicators is essential to improve EC management and outcome. "Immortality" of most cancer cells is dependent on telomerase, but the role of associated proteins in the endometrium is poorly understood. The Cancer Genome Atlas data highlighted telomere/telomerase associated genes (TTAGs) with prognostic relevance in the endometrium, and a recent in silico study identified a group of TTAGs and proteins as key regulators within a network of dysregulated genes in EC. We characterise relevant telomere/telomerase associated proteins (TTAPs) NOP10, NHP2, NOP56, TERF1, TERF2 and TERF2IP in the endometrium using quantitative polymerase chain reaction (qPCR) and immunohistochemistry (IHC). qPCR data demonstrated altered expression of multiple TTAPs; specifically, increased NOP10 (p = 0.03) and reduced NHP2 (p = 0.01), TERF2 (p = 0.01) and TERF2IP (p < 0.003) in EC relative to post-menopausal endometrium. Notably, we report reduced NHP2 in EC compared to post-menopausal endometrium in qPCR and IHC (p = 0.0001) data; with survival analysis indicating high immunoscore is favourable in EC (p = 0.0006). Our findings indicate a potential prognostic role for TTAPs in EC, particularly NHP2. Further evaluation of the prognostic and functional role of the examined TTAPs is warranted to develop novel treatment strategies.
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Tumors of the Female Reproductive Organs. Fam Med 2022. [DOI: 10.1007/978-3-030-54441-6_112] [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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Portela S, Cunningham A, Laios A, Hutson R, Theophilou G. Breast Cancer Patients at Increased Risk of Developing Type II Endometrial Cancer: Relative and Absolute Risk Estimation and Implications for Counseling. Cureus 2021; 13:e12981. [PMID: 33659121 PMCID: PMC7920226 DOI: 10.7759/cureus.12981] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
Abstract
Introduction Breast cancer (BC) is a recognized risk factor for endometrial cancer (EC). Emerging literature indicates that it confers a higher risk of type II EC (T2EC) than type I EC (T1EC). Although some surgeons offer a prophylactic hysterectomy to BC patients referred for risk-reducing bilateral salpingo-oophorectomy, insufficient evidence prevents this from being the standard practice. We aimed to quantify their absolute risk and relative risk (RR) of developing both EC subtypes and identify a higher-risk group that could be considered for prophylactic hysterectomy. Methodology This retrospective service evaluation compared patients diagnosed with BC between 2008 and 2014, who subsequently developed EC within 10 years to those who did not. Absolute risk and RR were calculated using the numbers of regional BC and EC cases within this group, alongside 2009 UK female population and EC incidence statistics. Binary logistic regression generated adjusted odds ratios (ORs) for patient- and disease-specific variables. Results A total of 45 BC patients developed EC, 24 had T1EC and 21 had T2EC. Their RR of developing EC was greater than that of the general population (RR: 12.44, p < 0.0001). Notably, this was higher for T2EC (RR: 33.96, p < 0.001) than T1EC (RR: 8.63, p < 0.0001). Nonetheless, the absolute risk remained low. Tamoxifen exposure was significantly more prevalent among T2EC patients (adjusted OR: 79.61, p = 0.003). Increased age at BC diagnosis was associated with T1EC (adjusted OR: 1.10, p = 0.043) and T2EC (adjusted OR: 1.13, p = 0.03). Neither smoking status nor family history of BC was significantly associated with any outcome. Conclusion Women with BC were more likely to develop T2EC than T1EC, and although the absolute risk was low, the cumulative risk was substantial enough to warrant vigilance. Tamoxifen exposure was significantly predictive of EC, particularly T2EC, and might facilitate risk estimation. Older women at BC diagnosis who receive tamoxifen treatment should be screened and closely monitored for EC. However, given the limitations of normal screening methods for the detection of T2EC, counseling for a prophylactic hysterectomy should also be considered. Clarification of the menopausal status will help make more meaningful recommendations.
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Affiliation(s)
- Sara Portela
- Gynaecological Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, GBR
| | - Aimee Cunningham
- Gynaecological Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, GBR
| | - Alexandros Laios
- Gynaecological Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, GBR
| | - Richard Hutson
- Gynaecological Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, GBR
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Mandato VD, Torricelli F, Mastrofilippo V, Palicelli A, Ciarlini G, Pirillo D, Annunziata G, Aguzzoli L. Accuracy of preoperative endometrial biopsy and intraoperative frozen section in predicting the final pathological diagnosis of endometrial cancer. Surg Oncol 2020; 35:229-235. [PMID: 32932219 DOI: 10.1016/j.suronc.2020.09.003] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2020] [Revised: 06/19/2020] [Accepted: 09/06/2020] [Indexed: 10/23/2022]
Abstract
BACKGROUND Histotype and grade of endometrial cancer (EC) are prognostic factors of nodal involvement and thus of survival. Preoperative biopsy (PB) and intraoperative frozen section (FS) are usually used to guide surgical staging on which the choice of adjuvant therapy will be based successively. OBJECTIVE The aim of this study was to assess the agreement rate between PB and FS with final diagnosis (FD) in a series of surgically resected EC. MATERIALS All patients submitted to hysterectomy for EC or atypical endometrial hyperplasia in the Reggio Emilia Province hospitals from 2007 to 2018 were included. Concordance rate differences in histotype, grading, myoinvasion, risk of recurrence between PB, FS and FD were assessed with Fisher's exact test and Mc Nemar contingency test. RESULTS A total of 352 patients were identified. For 345 patients it was possible to compare PB and FD results. FS examination was performed in 201/352 (57%) cases, while for 21/352 (6%) patients only an intraoperative macroscopic evaluation was done; in the remaining women, FS-exam was omitted. In 14/201 (7%) cases the tumor wasn't grossly identifiable and the random FS-sampling wasn't able to find the tumor site. High diagnostic concordance of tumor type between PB and FD was observed: no significant differences were registered in type 1 and type 2-endometrial cancer identification (83%, 73%, p = 0.121). Significant differences (p = 0.005) were observed comparing FS and FD results: 95% of type 1-ECs were correctly diagnosed by FS, while only 76% of type 2-ECs received a correct diagnosis on FS. PB showed a concordance with FD among tumor grading close to 55% whilst concordance achieved 71% grouping low grade (G1-G2) EC. No significant differences in FS and FD concordance rate were observed between tumor grades. Concordance for low grade was significantly higher than for high grade ECs (89% vs 50%, respectively, p value = 0.014). The concordance rate in evaluating the myoinvasion status between FS and FD was 80% (n: 199 patients), reaching 99% after combining the first 2 groups (0-49% vs ≥ 50%). Twenty-two cases underwent only intraoperative macroscopic evaluation of the myoinvasion, with an accuracy of 91%: only in 1 case the invasion of the cervical stroma was not detected (Stage II), and 1 case the patient was overstaged as Ib. Discrepancies were observed in FS capacity to correctly predict the final ESMO risk group in stage I patients: FS resulted particularly reliable in predicting a low-risk (concordance with FD: 91%) while the accuracy sharply decreased for intermediate- and high-risk patients (62% and 40%, respectively). To investigate the usefulness of FS in EC management, we compared patients who underwent FS (FS-group) or not (no-FS-group). Especially for low risk patients, the FS significantly increased the adequacy of surgical treatment from 53% (no-FS-group) to 72% (FS-group) (p = 0.016). CONCLUSIONS FS remains a useful tool to tailor surgery in EC-patients, avoiding secondary surgery to complete staging particularly in patients with AH + AHBA, low and intermediate risk ECs that could benefit from adjuvant therapy.
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Affiliation(s)
- Vincenzo Dario Mandato
- Unit of Obstetrics and Gynaecology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy.
| | - Federica Torricelli
- Laboratory of Translational Research, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Valentina Mastrofilippo
- Unit of Surgical Gynecol Oncology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Andrea Palicelli
- Pathology Unit, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Gino Ciarlini
- Unit of Surgical Gynecol Oncology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Debora Pirillo
- Unit of Obstetrics and Gynaecology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Gianluca Annunziata
- Unit of Obstetrics and Gynaecology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Lorenzo Aguzzoli
- Unit of Surgical Gynecol Oncology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
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11
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Body Image, Sexuality, and Sexual Functioning in Women With Gynecologic Cancer: An Integrative Review of the Literature and Implications for Research. Cancer Nurs 2020; 44:E252-E286. [PMID: 32332264 DOI: 10.1097/ncc.0000000000000818] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
BACKGROUND Cervical and uterine cancers are common in women. Diagnosis and treatment of these cancers can lead to significant issues with body image, sexuality, and sexual functioning. A comprehensive review can improve understanding of these 3 concepts, in turn enhancing identification and management. OBJECTIVES To (1) present the qualitative, descriptive, and correlational research literature surrounding body image, sexuality, and sexual functioning in women with uterine and cervical cancer; (2) identify gaps in the literature; and (3) explore the implications of the findings for future research. METHODS A comprehensive search of the literature was undertaken by searching PubMed, CINAHL, and PsycINFO using predetermined subject headings, keywords, and exploded topics. After a comprehensive evaluation using specific criteria, 121 articles were reviewed. RESULTS Qualitative studies provided information about women's issues with body image, sexuality, and sexual functioning, whereas quantitative studies focused primarily on sexual functioning. The literature lacks correlational studies examining body image and sexuality. Significant issues regarding communication and quality of life were noted, and few studies were based on clear conceptual models. CONCLUSION The state of the science gleaned from this review reveals that while much is known about sexual functioning, little is known about body image and sexuality. IMPLICATIONS FOR PRACTICE Further work is warranted to develop conceptual models and research on body image, sexuality, and sexual functioning as a foundation for interventions to improve quality of life.
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Horn LC, Höhn AK, Krücken I, Stiller M, Obeck U, Brambs CE. Mesonephric-like adenocarcinomas of the uterine corpus: report of a case series and review of the literature indicating poor prognosis for this subtype of endometrial adenocarcinoma. J Cancer Res Clin Oncol 2020; 146:971-983. [PMID: 31927619 DOI: 10.1007/s00432-019-03123-7] [Citation(s) in RCA: 38] [Impact Index Per Article: 7.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2019] [Accepted: 12/26/2019] [Indexed: 02/06/2023]
Abstract
PURPOSE Endometrial mesonephric-like adenocarcinoma (ML-AC) represents a recently recognized subtype of endometrial adenocarcinoma (AC) associated with a subtle immunophenotype with a characteristic KRAS-mutation. Detailed clinico-pathologic analyses and prognostic data on ML-AC are limited. METHODS We report a series of four cases with histopathological, immunohistochemical, and molecular analyses. These cases as well as the data of previously published cases were reviewed for clinico-pathologic variables and clinical follow-up information. RESULTS Forty cases of ML-AC were identified. ML-AC represents about 1% of all endometrial carcinomas. Similar to other types of endometrial AC, vaginal bleeding was the leading presenting symptom, and the mean age was 60.0 years (range 31-91). More than a half of the patients presented with locally advanced disease (≥ FIGO stage II) at time of diagnosis, developed a recurrence or died of the disease within a mean follow-up period of 24.7 months (range 3-144.5 months). The most common site of distant disease was pulmonary involvement. Microscopically, ML-ACs present with mixed morphology and show a co-expression of so-called mesonephric and Müllerian markers, suggesting a Müllerian origin of the tumors. Immunostaining for PD-L1 was negative in all tested cases, using different antibodies against PD-L1. Retained staining for mismatch repair proteins on immunohistochemistry and a POLE-mutation suggest a copy number low phenotype within the molecular classification of endometrial carcinomas. Almost all cases showed a KRAS-mutation at codon 12 (mostly G12V). CONCLUSION Uterine ML-AC represents a distinct subtype of invasive endometrial AC, associated with KRAS-mutations and characteristic immunohistochemical findings. Clinically, ML-AC may show an aggressive behavior with a high rate of recurrent disease and a substantial risk for distant metastatic disease, especially to the lungs.
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Affiliation(s)
- Lars-Christian Horn
- Division of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig, Liebigstrasse 26, 04103, Leipzig, Germany.
| | - Anne Kathrin Höhn
- Division of Gynecologic, Breast and Perinatal Pathology, Institute of Pathology, University Hospital Leipzig, Liebigstrasse 26, 04103, Leipzig, Germany
| | - Irene Krücken
- Division Molecular Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany
| | - Mathias Stiller
- Division Molecular Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany
| | - Ulrike Obeck
- Division Molecular Pathology, Institute of Pathology, University Hospital Leipzig, Leipzig, Germany
| | - Christine E Brambs
- Department of Obstetrics and Gynecology, Technical University Munich, Munich, Germany
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Shanmugam S, Thanikachalam R, Murugan A. Comparative Study of Laparoscopic versus Conventional Open Surgical Staging Procedure for Endometrial Cancer: Our Institutional Experience. Gynecol Minim Invasive Ther 2020; 9:29-33. [PMID: 32090010 PMCID: PMC7008649 DOI: 10.4103/gmit.gmit_82_19] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/24/2019] [Revised: 10/21/2019] [Accepted: 11/28/2019] [Indexed: 11/24/2022] Open
Abstract
Objective: The aim of this study was to compare laparoscopic surgical staging of endometrial cancer with conventional open methods. Materials and Methods: The retrospective data were collected from 90 endometrial cancer patients who were operated between 2013 and 2018 in our government institution. The safety and morbidity of the two groups were compared based on mean operative time, blood loss, intraoperative complications, postoperative complication, etc., and the results were analyzed. Statistical analysis was performed using IBM SPSS statistics version 20. Clinical and pathologic factors were compared between two groups with Fisher's exact test and Student's t-test for data analysis. The survival data were analyzed using Kaplan–Meier survival curves. P < 0.05 was considered statistically significant. Results: Thirty-two patients underwent laparoscopic staging, 45 underwent laparotomy, and 13 cases lap converted to open surgery. The mean operative time for the laparoscopic procedure was lower than the open procedure (P = 0.001). The mean hospital stay of patients who underwent laparoscopic staging was around 7.1 days significantly less compared to the laparotomy group. Intraoperative blood loss of patients undergoing laparoscopic surgery was significantly less than that of the laparotomy group (P = 0.015). There was no statistically significant difference in nodal retrieval between laparotomy and laparoscopy group (P = 0.172). The mean duration of hospitalization was statistically significantly greater in the laparotomy group than the laparoscopic group (13 and 7 days, P < 0.001). Based on the Kaplan–Meier survival curve, there was no difference in survival rates between the groups. Median follow-up duration was 32 months. Conclusion: Laparoscopic surgical staging is oncologically safe for the management of endometrial cancer with acceptable morbidity compared to the open approach with far less blood loss and shorter postoperative stay.
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Affiliation(s)
- Subbiah Shanmugam
- Department of Surgical Oncology, Government Royapettah Hospital, Kilpauk Medical College, Chennai, Tamil Nadu, India
| | - Rajkiran Thanikachalam
- Department of Surgical Oncology, Government Royapettah Hospital, Kilpauk Medical College, Chennai, Tamil Nadu, India
| | - Arul Murugan
- Department of Surgical Oncology, Government Royapettah Hospital, Kilpauk Medical College, Chennai, Tamil Nadu, India
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14
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Tumors of the Female Reproductive Organs. Fam Med 2020. [DOI: 10.1007/978-1-4939-0779-3_112-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
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15
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Kumar P, Singh G, Rai V. Evaluation of COMT Gene rs4680 Polymorphism as a Risk Factor for Endometrial Cancer. Indian J Clin Biochem 2020; 35:63-71. [PMID: 32071497 PMCID: PMC6995457 DOI: 10.1007/s12291-018-0799-x] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2018] [Accepted: 11/26/2018] [Indexed: 12/11/2022]
Abstract
Catechol-O-methyletransferase (COMT) enzyme is involved in the inactivation of catecholamine and catechol estrogens. Catechol estrogens have carcinogenic potential and DNA damaging ability. Several studies investigated COMT Val158Met polymorphism as risk factor for endometrial cancer but the results were inconclusive. Hence the objective of present study was to find out exact association between COMT gene Val158Met polymorphism and endometrial cancer by a meta-analysis. Pubmed, Google Scholar, Springer Link and Science Direct databases were searched for case-control articles which investigated COMT Val158Met polymorphism in endometrial cancer cases. All statistical analysis was performed using MetaAnalyst and Mix programs. The results of meta-analysis suggested that there were no association between COMT Val158Met polymorphism and endometrial cancer risk (allele contrast model-ORA vs. G = 0.97, 95% CI = 0.86-1.10, p = 0.67; co-dominant model-ORAG vs. GG = 0.91, 95% CI = 0.77-1.06, p = 0.23; homozygote model-ORAA vs. GG = 1.01, 95% CI = 0.84-1.19, p = 0.29; dominant model-ORAA+AG vs. GG = 0.93, 95% CI = 0.77-1.11, p = 0.43; recessive model-ORAA vs. AG+GG = 1.02, 95% CI = 0.89-1.20, p = 0.62). Publication bias was absent. Subgroup analysis based on source of controls was also performed. In conclusion, results of present meta-analysis showed no association between COMT Val158Met polymorphism and susceptibility to endometrial cancer.
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Affiliation(s)
- Pradeep Kumar
- Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, 222003 India
| | - Garima Singh
- Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, 222003 India
| | - Vandana Rai
- Human Molecular Genetics Laboratory, Department of Biotechnology, VBS Purvanchal University, Jaunpur, 222003 India
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16
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Shiomi M, Matsuzaki S, Kobayashi E, Hara T, Nakagawa S, Takiuchi T, Mimura K, Ueda Y, Tomimatsu T, Kimura T. Endometrial carcinoma in a gravid uterus: a case report and literature review. BMC Pregnancy Childbirth 2019; 19:425. [PMID: 31747899 PMCID: PMC6864955 DOI: 10.1186/s12884-019-2489-y] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2019] [Accepted: 09/04/2019] [Indexed: 02/08/2023] Open
Abstract
Background Endometrial carcinoma (EC) is rarely diagnosed during pregnancy. Therefore, the histopathological findings, clinical course, and gross appearance of the resected uterus during pregnancy are not well known. We present a case of EC diagnosed during pregnancy. In addition, we reviewed the literature dating from January 1995 to March 2019 for cases of EC diagnosed during pregnancy and within 15 months after pregnancy, and we discussed this topic to improve the understanding of this rare condition. Case presentation A 35-year-old woman underwent an urgent cesarean delivery in gestational week 35 due to antepartum bleeding caused by placenta previa. Hysterectomy was performed with the diagnosis of placenta accreta spectrum (PAS). Remarkably, the postoperative gross and histopathological examinations revealed an endometrioid adenocarcinoma (grade 1). The histopathological findings revealed a pattern similar to that of EC not related with pregnancy. Immunohistochemistry revealed an overexpression of the estrogen and progesterone receptors; however, the p53 expression was negative. We performed laparoscopic bilateral salpingo-oophorectomy and pelvic lymphadenectomy 102 days after the cesarean hysterectomy, and confirmed surgical stage IA without metastases. Our patient has had no recurrence in 4 years after the cesarean delivery. An electronic search of the literature revealed 25 cases of EC (including our case) diagnosed during or after pregnancy. Sixteen of the 25 patients were diagnosed after abortions in the first trimester, 9 were diagnosed within 14 months of childbirth, and our case was the first with diagnosis from a surgical specimen of peripartum hysterectomy due to the PAS. In 23 of the 25 cases endometrioid adenocarcinoma grade 1 to 2 was found, and it seemed to have a good prognosis. Conclusion The present findings suggest that careful examination of a resected uterus is essential, even when surgery is performed for an obstetric indication. Our case is an extremely rare case of EC during pregnancy; the histopathological pattern was similar to that of typical EC, and no recurrence was noted. The high levels of estrogen and progesterone during pregnancy did not seem to promote tumor progression in our case.
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Affiliation(s)
- Mayu Shiomi
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Shinya Matsuzaki
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
| | - Eiji Kobayashi
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Takeya Hara
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Satoshi Nakagawa
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tsuyoshi Takiuchi
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Kazuya Mimura
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Yutaka Ueda
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Takuji Tomimatsu
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
| | - Tadashi Kimura
- Department of Obstetrics and Gynecology, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan
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17
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Endometrial Cancer General Perspectives, Epidemiology. CURRENT OBSTETRICS AND GYNECOLOGY REPORTS 2019. [DOI: 10.1007/s13669-019-00272-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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Rosen MW, Tasset J, Kobernik EK, Smith YR, Johnston C, Quint EH. Risk Factors for Endometrial Cancer or Hyperplasia in Adolescents and Women 25 Years Old or Younger. J Pediatr Adolesc Gynecol 2019; 32:546-549. [PMID: 31226466 DOI: 10.1016/j.jpag.2019.06.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 05/14/2019] [Accepted: 06/10/2019] [Indexed: 02/07/2023]
Abstract
STUDY OBJECTIVE To evaluate characteristics of young women with endometrial hyperplasia or cancer. DESIGN Retrospective chart review. SETTING Tertiary care referral center. PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES We included 10- to 25-year-old young women seen at a single institution between 2006 and 2017 with International Classification of Diseases 9th and 10th revision codes for endometrial cancer or hyperplasia (cases), or who underwent an endometrial biopsy with other benign pathologic diagnoses (controls). Exclusions included a diagnosis of Lynch syndrome. Comparisons were made using χ2, Fisher exact, and nonparametric Wilcoxon rank tests. RESULTS Sixty-nine patients were identified: 13 cases, 54 controls, and 2 exclusions. Of the 13 cases, 3 had endometrial cancer, 5 had complex atypical hyperplasia (now called endometrioid intraepithelial neoplasia), and 5 had hyperplasia without atypia. A higher proportion of cases had a body mass index (BMI) greater than 30, compared with controls (76.9% vs 40.4%; P < .03). The proportion of patients who had a BMI greater than 30 and were smokers was significantly higher among cases (38.5% vs 9.3%; P < .02). The proportion of patients with a history of polycystic ovary syndrome (PCOS) and smoking was also significantly different between groups (30.8% vs 3.7%; P < .01). CONCLUSION In women aged 25 years and younger with endometrial sampling, a BMI greater than 30 was statistically more common in patients with endometrioid intraepithelial neoplasia or cancer. Although smoking or PCOS alone was not related to endometrial hyperplasia or cancer in this small cohort study, there might be a relationship between endometrial abnormalities and multiple exposures, including smoking and BMI greater than 30 or smoking and a history of PCOS.
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Affiliation(s)
- Monica W Rosen
- Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan.
| | - Julia Tasset
- University of Michigan Medical School, Ann Arbor, Michigan; Department of Obstetrics and Gynecology, University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Emily K Kobernik
- Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan
| | - Yolanda R Smith
- Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan
| | - Carolyn Johnston
- Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan
| | - Elisabeth H Quint
- Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan
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Saeki H, Hlaing MT, Horimoto Y, Kajino K, Ohtsuji N, Fujino K, Terao Y, Hino O. Usefulness of immunohistochemistry for mismatch repair protein and microsatellite instability examination in adenocarcinoma and background endometrium of sporadic endometrial cancer cases. J Obstet Gynaecol Res 2019; 45:2037-2042. [DOI: 10.1111/jog.14061] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Accepted: 06/23/2019] [Indexed: 01/24/2023]
Affiliation(s)
- Harumi Saeki
- Department of Pathology and OncologyJuntendo University School of Medicine Tokyo Japan
| | - May T. Hlaing
- Department of Pathology and OncologyJuntendo University School of Medicine Tokyo Japan
| | - Yoshiya Horimoto
- Department of Pathology and OncologyJuntendo University School of Medicine Tokyo Japan
- Department of Breast OncologyJuntendo University School of Medicine Tokyo Japan
| | - Kazunori Kajino
- Department of Pathology and OncologyJuntendo University School of Medicine Tokyo Japan
| | - Naomi Ohtsuji
- Department of Pathology and OncologyJuntendo University School of Medicine Tokyo Japan
| | - Kazunari Fujino
- Department of Obstetrics and GynecologyJuntendo University School of Medicine Tokyo Japan
| | - Yasuhisa Terao
- Department of Obstetrics and GynecologyJuntendo University School of Medicine Tokyo Japan
| | - Okio Hino
- Department of Pathology and OncologyJuntendo University School of Medicine Tokyo Japan
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20
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Camuzcuoğlu A, Sezgin B, Çelik H, Camuzcuoğlu H. Evaluation of serum M30 and M65 activity in patients with stage-I endometrial cancer. J OBSTET GYNAECOL 2019; 39:1112-1116. [PMID: 31177876 DOI: 10.1080/01443615.2019.1586855] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
We aimed to analyse the prognostic value of serum oxidative stress parameters and apoptotic markers of serum M30/65 levels in endometrial cancer patients. Serum M30/65 levels and oxidative stress parameters were evaluated in 52 women with stage I endometrial cancer (n = 26) and a control group of healthy females (n = 26). The total antioxidant status (p = .002), oxidative stress index (p = .003) and serum M30/65 levels (p < .001) were significantly higher in women with stage-I endometrial cancer in comparison to the control group. Furthermore, serum M30/65 levels were significantly lower on postoperative day 8, compared to preoperative levels (p = .001 and p < .001, respectively), in the endometrial cancer group. Although impaired apoptotic activity plays a crucial role in the aetiopathogenesis of endometrial cancer, oxidative stress may be instrumental in malignant transformation. We concluded that measurement of M30/65 levels would be beneficial in the follow-up of women with endometrial cancer. Impact Statement What is already known on this subject: Although M30 has been evaluated as a marker of apoptosis in tissue samples from women with endometrial cancer (EC), no previous studies have simultaneously analysed serum M30 and M65 levels and oxidative stress in patients with stage-I EC. What the results of this study add: Total antioxidant status (TAS), total oxidant status (TOS), oxidative stress index (OSI) and serum M30/65 levels were significantly higher in women with stage I EC in comparison to the control group. Furthermore, serum M30/65 levels were significantly lower on postoperative day 8, compared to preoperative levels, in the EC group. The fact that pre-operative M30/M65 levels were higher than the post-operative levels may be very important in early-stage EC What the implications are of these findings for clinical practice and/or further research: Although impaired apoptotic activity plays a crucial role in the aetiopathogenesis of EC, oxidative stress may be instrumental in malignant transformation. The fact that serum M30/M65 levels decreased in accordance with the reduction of post-operative tumour burden led us to conclude that measurement of M30/65 levels would be beneficial in the follow-up of women with EC.
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Affiliation(s)
- Aysun Camuzcuoğlu
- Obstetrics and Gynecology, Private Adatıp Sakarya Hospital , Sakarya , Turkey
| | - Burak Sezgin
- Obstetrics and Gynecology, Muğla Sıtkı Koçman University Faculty of Medicine , Muğla , Turkey
| | - Hakim Çelik
- Physiology, Harran University Faculty of Medicine , Sanliurfa , Turkey
| | - Hakan Camuzcuoğlu
- Private Adatıp Sakarya Hospital, Gynecologic Oncology , Sakarya , Turkey
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21
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Nithin KU, Sridhar MG, Srilatha K, Habebullah S. CA 125 is a better marker to differentiate endometrial cancer and abnormal uterine bleeding. Afr Health Sci 2018; 18:972-978. [PMID: 30766562 PMCID: PMC6354887 DOI: 10.4314/ahs.v18i4.17] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Background Incidence of endometrial cancer in India is increasing due to lifestyle changes and obesity. As 5 year survival rate of cancer confined to uterus is good, there is need for serum tumor marker for early diagnosis. This study was designed to identify a tumor marker which differentiate endometrial carcinoma and abnormal uterine bleeding (AUB) because common presentation of endometrial carcinoma is AUB. Objectives To estimate and compare serum prolactin, Cancer Antigen 125 (CA-125), Cancer Antigen 15-3 (CA15-3), and Carcino embryonic antigen (CEA) levels in patients with endometrial cancer and abnormal uterine bleeding; To evaluate the role of these markers in diagnosing endometrial cancer. Methodology Thirty eight patients with endometrial cancer and 40 patients with AUB were recruited in this study. Serum prolactin, CA 125, CEA, and CA 15-3 levels were estimated in both groups. Results The levels of CA 15-3, CA 125, CEA, and prolactin were increased in endometrial carcinoma patients, on comparison with AUB patients. CA 125 alone was found to be a better marker to detect endometrial cancer with 52.63% sensitivity, 80.00% specificity. Conclusion As individual tumor marker, serum CA 125 has the ability to detect endometrial cancer in patients with abnormal uterine bleeding.
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Affiliation(s)
| | | | | | - S Habebullah
- Department of Obstetrics and Gynecology, Jawaharlal Institute of Post graduate Medical Education and Research, Puducherry - 605006
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22
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Gao Y, Dai X, Lee AC, Wise MR, Shen F, Chen Q. Body Mass Index is Negatively Associated with Endometrial Cancer Stage, Regardless of Subtype and Menopausal Status. J Cancer 2018; 9:4756-4761. [PMID: 30588261 PMCID: PMC6299378 DOI: 10.7150/jca.21137] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2017] [Accepted: 07/10/2017] [Indexed: 12/19/2022] Open
Abstract
Objective: Obesity is one of the common risk factors for developing of endometrial cancer and is negatively associated with its survival, although this result is controversial. Endometrial cancer stages range from stage I, which has better clinical outcomes to stage IV, which has poorer clinical outcomes. Endometrial cancer traditionally divides into type 1 and type 2 dependent on histology which has different clinical outcomes. In this study we investigated whether obesity is associated with the stages of endometrial cancer taking into account subtypes of cancer and menopausal status. Methods: Data on 1,104 women with endometrial cancer were retrospectively collected from the largest women's hospital in China and analysed. Data included age at diagnosis, body mass index (BMI), histology of cancer and menopausal status. Results: The BMI in patients with stage I endometrial cancer was significantly higher than that in patients with stage II or III or IV (p=0.0001). However, there was no statistical difference in BMI between patients with stage II, and stage III endometrial cancer. This negative association was persisted with type 1 and type 2 endometrial cancer (p=0.1989) and premenopausal and post-menopausal status (p=0.4342). In addition, the proportion of over-weight or obese women in type1 endometrial cancer with stage I was not different to type 2 endometrial cancer with stage I. Conclusion: Our data demonstrate that BMI is negatively associated with endometrial cancer in early stage regardless of subtypes of cancer, menopausal status and obesity may be also a potential risk factor for developing type 2 endometrial cancer.
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Affiliation(s)
- Yifei Gao
- The Hospital of Obstetrics & Gynaecology, Fudan University, China
| | - Xujing Dai
- The Hospital of Obstetrics & Gynaecology, Fudan University, China
| | - Arier C Lee
- Section of Epidemiology and Biostatistics, School of Population Health, The University of Auckland, New Zealand
| | - Michelle R Wise
- Department of Obstetrics & Gynaecology, FMHS, University of Auckland, New Zealand
| | - Fang Shen
- The Hospital of Obstetrics & Gynaecology, Fudan University, China
| | - Qi Chen
- The Hospital of Obstetrics & Gynaecology, Fudan University, China.,Department of Obstetrics & Gynaecology, FMHS, University of Auckland, New Zealand
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23
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Jiang XH, Yao ZY, He X, Zhang JB, Xie K, Chen J, Cao M, Zhang J, Yie SM. Clinical significance of plasma anti-TOPO48 autoantibody and blood survivin-expressing circulating cancer cells in patients with early stage endometrial carcinoma. Arch Gynecol Obstet 2018; 299:229-237. [PMID: 30341503 DOI: 10.1007/s00404-018-4938-7] [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] [Received: 05/16/2018] [Accepted: 09/05/2018] [Indexed: 12/11/2022]
Abstract
PURPOSE To examine the clinical significance of an autoantibody (AAb) against a novel tumor-associated antigen (TAA) derived from human DNA-topoisomerase I, termed as TOPO48 AAb, and peripheral blood survivin-expressing circulating cells (CCC) in patients with early stage endometrial cancer (EC). METHODS Blood samples were collected from 80 patients with early stage EC and 80 age-matched healthy subjects. Plasma levels of the TOPO48 AAb were measured with a specific antibody capture enzyme-linked immunosorbent assay (ELISA) and blood survivin-expressing CCC assessed with a reverse transcription-polymerase chain reaction products based on a hybridization-enzyme-linked immunosorbent assay (RT-PCR-ELISA). Sixty patients were followed up for 36 months after the initial assay test. RESULTS There were 75% and 60% samples with positive levels of the TOPO48 AAb and survivin-expressing CCC in the cancer patients, respectively. However, the cumulative positive rate of combination of the two markers was increased to 93.3% with 0.927 (95% CI 0.871-0.984) of area under the curve (AUC) in receiver operating characteristic (ROC) curve analysis. During the follow-up period, patients with positive TOPO48 AAb but negative surviving-expressing CCC had a higher survival rate and a longer survival time than those with negative AAb but positive CCC (P = 0.01). CONCLUSIONS The combination of TOPO48 AAb and survivin-expressing CCC may be used as a novel recipe to improve the efficiency of early diagnosis and provide more accurate prognostic prediction in patients with early stage EC.
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Affiliation(s)
- Xiao-Hui Jiang
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Human Sperm Bank, West China Second University Hospital of Sichuan University, Chengdu, 610041, Sichuan, People's Republic of China
| | - Zou-Ying Yao
- Department of Traditional Chinese Medicine, Lishui Central Hospital, Lishui, 323000, Zhejiang, People's Republic of China
| | - Xu He
- Core Laboratory, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, 610072, Sichuan, People's Republic of China
| | - Jian-Bo Zhang
- Core Laboratory, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, 610072, Sichuan, People's Republic of China
| | - Ke Xie
- Department of Oncology, Sichuan Academy of Medical Sciences Sichuan Provincial People's Hospital, Chengdu, 610072, Sichuan, People's Republic of China
| | - Jie Chen
- Core Laboratory, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, 610072, Sichuan, People's Republic of China
| | - Mei Cao
- Core Laboratory, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, 610072, Sichuan, People's Republic of China
| | - Jian Zhang
- Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 610041, Sichuan, People's Republic of China
| | - Shang-Mian Yie
- Chengdu Cancer Bioengineering Research Institute, 37 Twelve Bridge Road, Chengdu, 610048, Sichuan, People's Republic of China.
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The cigarette smoke components induced the cell proliferation and epithelial to mesenchymal transition via production of reactive oxygen species in endometrial adenocarcinoma cells. Food Chem Toxicol 2018; 121:657-665. [PMID: 30236600 DOI: 10.1016/j.fct.2018.09.023] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2017] [Revised: 09/11/2018] [Accepted: 09/15/2018] [Indexed: 12/27/2022]
Abstract
Cigarette smoke (CS) causes about 480,000 deaths each year worldwide and is well-known to have harmful effects on the human body, leading to heart disease, stroke, lung cancer, and cardiovascular problems. In the present study, the effects of acrylonitrile (AN), benzo(a)pyrene (B(a)P), formaldehyde (FOR), isoprene (ISO), nicotine-derived nitrosamine ketone (NNK), which are the main components of CS, on the proliferation, invasion, and the epithelial-mesenchymal transition (EMT) process of human Ishikawa endometrial adenocarcinoma cells were investigated. Treating Ishikawa cells with CS components resulted in increased cell growth and altered expression of cell cycle-related genes: the protein expression of cyclin D & E increased, while the levels of p21 & p27 were reduced following treatment of these five CS components. In addition, CS components increased the invasion capacity of Ishikawa cells. The expression of the epithelial markers, E-cadherin and occludin, were significantly decreased, while the expression of the mesenchymal marker, N-cadherin, was significantly increased by CS components. In dichloro-dihydro-fluorescein diacetate (H2DCF-DA) assay, ROS production increased by treatment of CS components. The CS components activated the ROS-p38 MAPK-EMT pathway by increasing the level of phosphorylated p38 MAPK and p44/42 (ERK1/2), and by up-regulating Snail and Slug, the transcription factors for EMT. Taken together, these results indicate that CS components can promote progression of endometrial adenocarcinoma via increasing cell proliferation and the ROS-mediated EMT process.
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Raventós-Tato RM, de la Torre-Fernández de Vega J, Sánchez-Iglesias JL, Díaz-Feijoó B, Sabadell J, Pérez-Benavente MA, Gil-Moreno A. Surgical approaches in women with endometrial cancer with a body mass index greater than 35 kg/m2. J Obstet Gynaecol Res 2018; 45:195-202. [DOI: 10.1111/jog.13789] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Accepted: 07/28/2018] [Indexed: 01/14/2023]
Affiliation(s)
- Rut M. Raventós-Tato
- Unit of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hospital Materno-Infantil Vall d'Hebron; Universitat Autònoma de Barcelona; Barcelona Spain
| | - Javier de la Torre-Fernández de Vega
- Unit of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hospital Materno-Infantil Vall d'Hebron; Universitat Autònoma de Barcelona; Barcelona Spain
| | - José L. Sánchez-Iglesias
- Unit of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hospital Materno-Infantil Vall d'Hebron; Universitat Autònoma de Barcelona; Barcelona Spain
| | - Berta Díaz-Feijoó
- Unit of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hospital Materno-Infantil Vall d'Hebron; Universitat Autònoma de Barcelona; Barcelona Spain
| | - Jordi Sabadell
- Unit of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hospital Materno-Infantil Vall d'Hebron; Universitat Autònoma de Barcelona; Barcelona Spain
| | - María A. Pérez-Benavente
- Unit of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hospital Materno-Infantil Vall d'Hebron; Universitat Autònoma de Barcelona; Barcelona Spain
| | - Antonio Gil-Moreno
- Unit of Gynecologic Oncology, Department of Obstetrics and Gynecology, Hospital Materno-Infantil Vall d'Hebron; Universitat Autònoma de Barcelona; Barcelona Spain
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Torricelli F, Nicoli D, Bellazzi R, Ciarrocchi A, Farnetti E, Mastrofilippo V, Zamponi R, La Sala GB, Casali B, Mandato VD. Computational development of a molecular-based approach to improve risk stratification of endometrial cancer patients. Oncotarget 2018; 9:25517-25528. [PMID: 29876005 PMCID: PMC5986657 DOI: 10.18632/oncotarget.25354] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2018] [Accepted: 04/25/2018] [Indexed: 11/25/2022] Open
Abstract
Histological classification and staging are the gold standard for the prognosis of endometrial cancer (EC). However, in morphologically intermediate and doubtful cases this approach results largely insufficient, defining the need for better classification criteria. In this work we developed an algorithm that based on EC genetic alterations and in combination with the current histological classification, improves EC patients prognostic stratification, in particular in doubtful cases. A panel of 26 cancer related genes was analyzed in 89 EC patients and somatic functional mutations were investigated in association with different histology and outcome. An unsupervised hierarchical clustering analysis revealed that two groups of patients with different tumor grade and different prognosis can be distinguished by mutational profile. In particular, the mutational status of APC, CTNNB1, PIK3CA, PTEN, SMAD4 and TP53 resulted to be principal drivers of prognostic clustering. Consistently, a decisional tree generated by a data mining approach summarizes the consequential molecular criteria for patients prognostic stratification. The model proposed by this work provides the clinician with a tool able to support the prognosis of EC patients and consequently drives the choice of the most appropriated therapeutic strategy and follow up.
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Affiliation(s)
- Federica Torricelli
- Laboratory of Translational Research, Azienda USL Reggio Emilia-IRCCS, Reggio Emilia, Italy
| | - Davide Nicoli
- Laboratory of Molecular Biology, Azienda USL Reggio Emilia-IRCCS, Reggio Emilia, Italy
| | - Riccardo Bellazzi
- Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy
| | - Alessia Ciarrocchi
- Laboratory of Translational Research, Azienda USL Reggio Emilia-IRCCS, Reggio Emilia, Italy
| | - Enrico Farnetti
- Laboratory of Molecular Biology, Azienda USL Reggio Emilia-IRCCS, Reggio Emilia, Italy
| | - Valentina Mastrofilippo
- Unit of Surgical Gynecologic Oncology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Raffaella Zamponi
- Laboratory of Molecular Biology, Azienda USL Reggio Emilia-IRCCS, Reggio Emilia, Italy
| | - Giovanni Battista La Sala
- Unit of Obstetrics and Gynaecology, University of Modena and Reggio Emilia, Reggio Emilia, Italy
- Unit of Obstetrics and Gynaecology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
| | - Bruno Casali
- Laboratory of Molecular Biology, Azienda USL Reggio Emilia-IRCCS, Reggio Emilia, Italy
| | - Vincenzo Dario Mandato
- Unit of Obstetrics and Gynaecology, Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia, Reggio Emilia, Italy
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Thickened Endometrium in Postmenopausal Women With an Initial Biopsy of Limited, Benign, Surface Endometrium: Clinical Outcome and Subsequent Pathologic Diagnosis. Int J Gynecol Pathol 2018; 38:310-317. [PMID: 29750705 DOI: 10.1097/pgp.0000000000000525] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Endometrial biopsy or curetting is indicated for postmenopausal women with abnormal uterine bleeding and/or thickened endometrium. Often, endometrial biopsy or curetting yields limited benign surface endometrium, which may indicate insufficient sampling. This study addresses the clinical outcome and subsequent pathologic diagnoses in postmenopausal women who received this initial diagnosis. Among a total of 370 endometrial biopsy or curetting between 2012 and 2015, 192 (52%) were diagnosed as limited benign surface endometrial epithelium. The women ranged in age from 55 to 91 yr old. Their clinical presentations mainly included postmenopausal bleeding, pelvic pain, and enlarged uterus. Primarily because the initial report was interpreted as "benign," 108 (57%) had no subsequent follow-up. Interestingly, women with an increased endometrial thickness were more likely to receive repeat evaluation. Among the 84 women who underwent follow-up endometrial sampling, 6 (7%) had hyperplasia with atypia or malignancy, 21 (25%) had a repeat diagnosis of limited surface sample, 4 (5%) had insufficient materials, and 53 (63%) had other benign findings. Among the subset of women who did receive subsequent follow-up, endometrial atypia or malignancies are more likely found in those with increased body mass index. In conclusion, a slight majority of women with postmenopausal bleeding and/or thickened endometrium had an initial limited surface endometrial sample. Most had no subsequent endometrial sampling. Among those with subsequent follow-up, the majority had benign findings. The study highlights the inconsistencies in adequacy criteria for endometrial sampling and the lack of standardization of subsequent management.
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Minichromosome maintenance complex component 6 (MCM6) expression correlates with histological grade and survival in endometrioid endometrial adenocarcinoma. Virchows Arch 2017; 472:623-633. [PMID: 29243125 DOI: 10.1007/s00428-017-2278-9] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2017] [Revised: 11/30/2017] [Accepted: 12/04/2017] [Indexed: 12/16/2022]
Abstract
Minichromosome maintenance complex component 6 (MCM6) is involved in initiating DNA replication and is upregulated during licensed G0 phase of the cell cycle. This early expression permits its labeling of more proliferating cells than those by Ki-67. Here using a cohort of 89 endometrioid adenocarcinoma, we report findings made on the prognostic value of MCM6 based on immunohistochemical labeling index (LI) of the protein in comparison with that of Ki67 as no such information is currently available. Additionally, we examined the prognostic values of these markers based on their mRNA expression using a cohort of uterine corpus endometrial carcinoma (UCEC, n = 307) taken from The Cancer Genome Atlas (TCGA) database. Our evidence indicated the presence of a positive correlation between the LI of MCM6 and the histological grade of endometrioid endometrial adenocarcinoma (grade I, 66.7%; grade II, 75.3%; grade III, 81.4%; p < 0.001) and an inverse correlation between the LI of MCM6 and the overall and progression-free survival (p = 0.02 for both). The LI of Ki-67 correlated with grade (p < 0.001), but not survival. The MCM6 and Ki-67 inter-observer intra-class correlation coefficients were excellent: 0.84 (95% confidence interval, 0.83-0.91) and 0.84 (0.77-0.90), respectively. For in silico analyses of the TCGA cohort, both univariate and multivariate Cox analyses (p = 0.003 and p = 0.03, respectively) revealed high MCM6 mRNA Z-scores associated with reduced overall survival. This association was absent for Ki-67. MCM6 is thus a highly reproducible marker of poor prognosis in endometrial cancer. Evaluation of MCM6 should thus be considered in daily practice for risk stratification.
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Rizzo S, Femia M, Radice D, Del Grande M, Franchi D, Origgi D, Buscarino V, Mauro A, Bellomi M. Evaluation of deep myometrial invasion in endometrial cancer patients: is dual-energy CT an option? Radiol Med 2017; 123:13-19. [DOI: 10.1007/s11547-017-0810-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Accepted: 09/04/2017] [Indexed: 12/14/2022]
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Naki MM, Oran G, Tetikkurt SÜ, Sönmez CF, Türkmen İ, Köse F. Microcystic, elongated, and fragmented pattern of invasion in relation to histopathologic and clinical prognostic factors in endometrioid endometrial adenocarcinoma. J Turk Ger Gynecol Assoc 2017; 18:139-142. [PMID: 28890428 PMCID: PMC5590210 DOI: 10.4274/jtgga.2017.0016] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/01/2022] Open
Abstract
Objective: To investigate the association of microcystic, elongated, and fragmented (MELF) pattern of invasion with prognostic factors in endometrioid endometrial adenocarcinoma (EEA). Material and Methods: Stained tissue sections from 83 cases of EEA operated by the same gynecologic oncologist were reviewed to identify cases showing MELF-type invasion in this retrospective study. The association of MELF pattern with age, tumor grade, depth of myometrial invasion, and presence of lymphovascular space invasion (LVSI) was analyzed. Results: FIGO grade 2 and grade 1 tumors were evident in 53.0% and 38.6% of patients, respectively. Depth of myometrial invasion was <50% in 72.0% of patients, and LVSI was absent in 77.1%. MELF pattern was confirmed in 35 (42.2%) patients. Presence of MELF pattern was associated with significantly higher mean ± standard deviation age (62.9±6.9) years vs. 58.9±9.1 years, p=0.033), and found to be more likely in patients with high-grade tumor (FIGO grade III; 85.7% vs. 14.3%, p<0.001), deep (≥50%) myometrial invasion (78.3% vs. 21.7%, p<0.001), and presence of LVSI (94.7% vs. 5.3%, p<0.001) as compared with absence of MELF pattern. Conclusion: In conclusion, our findings revealed a high rate of MELF pattern among patients with EEA alongside the association of MELF pattern with poor prognostic factors such as high grade tumor, deep myometrial invasion, and LVSI.
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Affiliation(s)
- M Murat Naki
- Department of Obstetrics and Gynecology, Acıbadem University Faculty of Medicine, İstanbul, Turkey
| | - Gülbin Oran
- Department of Pathology, Medipol University Faculty of Medicine, İstanbul, Turkey
| | - Seza Ümit Tetikkurt
- Department of Pathology, Bağcılar Training and Research Hospital, İstanbul, Turkey
| | - Cavide Fatma Sönmez
- Department of Pathology, Bezmialem Vakıf University Faculty of Medicine, İstanbul, Turkey
| | - İlknur Türkmen
- Department of Pathology, Medipol University Faculty of Medicine, İstanbul, Turkey
| | - Faruk Köse
- Department of Obstetrics and Gynecology, Acıbadem University Faculty of Medicine, İstanbul, Turkey
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Kuribayashi Y, Nakagawa K, Sugiyama R, Motoyama H, Sugiyama R. Frequency of endometrial cancer and atypical hyperplasia in infertile women undergoing hysteroscopic polypectomy. J Obstet Gynaecol Res 2017; 43:1465-1471. [DOI: 10.1111/jog.13408] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2017] [Revised: 04/12/2017] [Accepted: 05/01/2017] [Indexed: 11/30/2022]
Affiliation(s)
| | - Koji Nakagawa
- Division of Reproductive Medicine; Sugiyama Clinic; Tokyo Japan
| | - Rie Sugiyama
- Reproductive Medicine and Surgery; Sugiyama Clinic Marunouchi; Tokyo Japan
| | - Hiroshi Motoyama
- Reproductive Medicine and Surgery; Sugiyama Clinic Marunouchi; Tokyo Japan
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Pabalan N, Kunjantarachot A, Ruangpratheep C, Jarjanazi H, Christofolini DM, Barbosa CP, Bianco B. Potential of RASSF1A promoter methylation as biomarker for endometrial cancer: A systematic review and meta-analysis. Gynecol Oncol 2017; 146:603-608. [PMID: 28669560 DOI: 10.1016/j.ygyno.2017.06.017] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Revised: 06/08/2017] [Accepted: 06/13/2017] [Indexed: 01/06/2023]
Abstract
BACKGROUND An epigenetic approach to explaining endometrial carcinogenesis necessitates good understanding of Ras association domain family 1 isoform A (RASSF1A) promoter methylation data from primary studies. AIMS Differential magnitude of reported associations between RASSF1A promoter methylation and endometrial cancer (EC) prompted a meta-analysis to obtain more precise estimates. METHODS Literature search yielded eight included articles. We calculated pooled odds ratios (OR) and 95% confidence intervals and subgrouped the data by race. Sources of heterogeneity were investigated with outlier analysis. RESULTS The pooled ORs indicated increased risk, mostly significant. The overall effect (OR 11.46) was reflected in the European outcome (OR 15.07). However, both findings were heterogeneous (I2=57-70%) which when subjected to outlier treatment, erased heterogeneity (I2=0%) and retained significance (OR 9.85-12.66). Significance of these pre- and post-outlier outcomes were pegged at P≤0.0001. Only the Asian pre-outlier (OR 6.85) and heterogeneous (I2=82%) outcome was not significant (P=0.12) but when subjected to outlier treatment, erased heterogeneity (I2=0%) and generated significance (OR 23.74, P≤0.0001). CONCLUSIONS Consistent increased risk associations underpinned by significance and robustness render RASSF1A with good biomarker potential for EC.
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Affiliation(s)
- Noel Pabalan
- Chulabhorn International College of Medicine, Thammasat University, Pathum Thani, Thailand.
| | | | | | - Hamdi Jarjanazi
- Environmental Monitoring and Reporting Branch, Ontario Ministry of the Environment and Climate Change, 125 Resources Road, Toronto, Ontario, Canada
| | - Denise Maria Christofolini
- Human Reproduction and Genetics Center, Department of Collective Health, Faculdade de Medicina do ABC, Santo André/SP, Brazil
| | - Caio Parente Barbosa
- Human Reproduction and Genetics Center, Department of Collective Health, Faculdade de Medicina do ABC, Santo André/SP, Brazil
| | - Bianca Bianco
- Human Reproduction and Genetics Center, Department of Collective Health, Faculdade de Medicina do ABC, Santo André/SP, Brazil
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33
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Tumors of the Female Reproductive Organs. Fam Med 2017. [DOI: 10.1007/978-3-319-04414-9_112] [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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Rezk M, Masood A, Dawood R. Perimenopausal bleeding: Patterns, pathology, response to progestins and clinical outcome. J OBSTET GYNAECOL 2016; 35:517-21. [PMID: 25383726 DOI: 10.3109/01443615.2014.977781] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
This prospective observational study was done on 400 perimenopausal patients who presented with abnormal uterine bleeding with selective endometrial lesions diagnosed on histopathology. Patients were followed to determine their response to progestin therapy and their final clinical outcome. The commonest bleeding pattern was menorrhagia (67.5%), the commonest pathology was simple endometrial hyperplasia without atypia (31%). 142 cases with non- atypical endometrial hyperplasia received progestin therapy with follow up, 100 cases (70.4%) experienced lesion regression, 38 cases (26.7%) experienced persistence and four cases (2.9%) experienced progression to atypia. Low dose progestin therapy (< 20 mg/day) was more effective when used for 4-5 months. Hysterectomy was done for 44 cases, due to atypical endometrial hyperplasia, persistence and progression of non atypical hyperplasia. Perimenopausal bleeding is mostly dysfunctional in origin but organic lesions remained a major concern which requires endometrial sampling with proper interpretation to achieve better clinical outcome.
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Affiliation(s)
- M Rezk
- a Department of Obstetrics and Gynecology , Faculty of Medicine, Menoufia University , Shibin Elkom, Menoufia , Egypt
| | - A Masood
- a Department of Obstetrics and Gynecology , Faculty of Medicine, Menoufia University , Shibin Elkom, Menoufia , Egypt
| | - R Dawood
- a Department of Obstetrics and Gynecology , Faculty of Medicine, Menoufia University , Shibin Elkom, Menoufia , Egypt
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35
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Hardcastle SJ, Glassey R, Salfinger S, Tan J, Cohen P. Factors influencing participation in health behaviors in endometrial cancer survivors. Psychooncology 2016; 26:1099-1104. [DOI: 10.1002/pon.4288] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2016] [Revised: 09/20/2016] [Accepted: 09/21/2016] [Indexed: 01/30/2023]
Affiliation(s)
- Sarah J. Hardcastle
- Health Psychology and Behavioural Medicine Research Group; Curtin University; Perth Australia
| | - Rachael Glassey
- School of Surgery; University of Western Australia; Perth Australia
| | | | - Jason Tan
- St John of God Hospital; Subiaco Perth Australia
| | - Paul Cohen
- St John of God Hospital; Subiaco Perth Australia
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36
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Walker AJ, Benrubi ID, Ward KK. Care of survivors of gynecologic cancers. World J Obstet Gynecol 2016; 5:140-149. [DOI: 10.5317/wjog.v5.i2.140] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/29/2015] [Revised: 11/16/2015] [Accepted: 02/24/2016] [Indexed: 02/05/2023] Open
Abstract
The number of cancer survivors is increasing and most healthcare providers will manage patients who have completed therapy for malignancy at some point. The care of survivors of gynecologic malignancies may seem daunting in a busy general gynecology practice. This paper intends to review the literature and suggest management of these women for the general gynecologist.
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37
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Li LH, Zhang PR, Cai PY, Li ZC. Histone deacetylase inhibitor, Romidepsin (FK228) inhibits endometrial cancer cell growth through augmentation of p53-p21 pathway. Biomed Pharmacother 2016; 82:161-6. [PMID: 27470351 DOI: 10.1016/j.biopha.2016.04.053] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2016] [Revised: 04/25/2016] [Accepted: 04/25/2016] [Indexed: 01/08/2023] Open
Abstract
OBJECTIVE Romidepsin (FK228), a Histone Deacetylase (HDAC) inhibitor, has been used for anti-cancer therapies. However, the anti-cancer effect of FK228 and its underlying mechanism in endometrial carcinoma (EC) have not been studied. The aime of this study was to investigate the anti-cancer effects of FK228 and the associated mechanism(s) in EC. METHODS Ishikawa and HEC-1-A endometrial cancer cells were treated with 8nM concentration of FK228 and cell growth was measured by XTT assay. The cell cycle distribution and cell death were measured by flow cytometry, immunofluorescence, respectively. The mNRA and protein expressions were analyzed by quantitative RT-PCR and western blot, respectively. RESULTS Based on assays carried out in EC cell lines, it was observed that FK228 inhibited EC cell proliferation in a dose and time-dependent manner. Furthermore, following treatment with FK228 for 48h, there were significant induction of apoptosis and cell cycle arrest at G0/G1 phase in EC cells. Moreover, FK228 treatment significantly increased the mRNA and protein expressions of p53, p21, cleaved caspases such as 3, 7 and 8 and PARP. Further, FK228 treatment increased the levels of acetylated histone H3 and H4 that confirms the HDAC inhibition. CONCLUSION In conclusion, FK228 inhibits EC tumor cell proliferation and induces apoptosis by activation caspase/PARP via the induction of p53/p21 signaling cascades, suggesting that FK228 is a potential therapeutic agent for EC.
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Affiliation(s)
- Lu-Hong Li
- Department of Obstetrics and Gynecology, Second Affiliated Hospital of Fujian Medical College, China.
| | - Pei-Ru Zhang
- Department of Obstetrics and Gynecology, Second Affiliated Hospital of Fujian Medical College, China
| | - Pei-Ya Cai
- Department of Obstetrics and Gynecology, Second Affiliated Hospital of Fujian Medical College, China
| | - Zhi-Chao Li
- Department of Radiology, Second Affiliated Hospital of Fujian Medical College, China
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38
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Yu X, Zhou B, Zhang Z, Lan Z, Chen P, Duan R, Zhang L, Xi M. Insertion/deletion polymorphism in IL1A
3′-UTR is associated with susceptibility to endometrial cancer in Chinese Han women. J Obstet Gynaecol Res 2016; 42:983-9. [PMID: 27136893 DOI: 10.1111/jog.12989] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Revised: 12/28/2015] [Accepted: 02/07/2016] [Indexed: 12/23/2022]
Affiliation(s)
- Xiuzhang Yu
- Department of Obstetrics and Gynecology; West China Second Hospital, Sichuan University; Chengdu China
| | - Bin Zhou
- Laboratory of Molecular Translational Medicine, West China Institute of Women and Children's Health; West China Second University Hospital, Sichuan University; Chengdu China
| | - Zhu Zhang
- Department of Obstetrics and Gynecology; West China Second Hospital, Sichuan University; Chengdu China
| | - Zhu Lan
- Department of Obstetrics and Gynecology; West China Second Hospital, Sichuan University; Chengdu China
| | - Peng Chen
- Department of Forensic Biology, West China School of Preclinical and Forensic Medicine; Sichuan University; Chengdu China
| | - Ruiqi Duan
- Department of Obstetrics and Gynecology; West China Second Hospital, Sichuan University; Chengdu China
| | - Lin Zhang
- Laboratory of Molecular Translational Medicine, West China Institute of Women and Children's Health; West China Second University Hospital, Sichuan University; Chengdu China
| | - Mingrong Xi
- Department of Obstetrics and Gynecology; West China Second Hospital, Sichuan University; Chengdu China
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El-Sharkawy M, El-Mazny A, Ramadan W, Hatem D, Abdel-Hafiz A, Hammam M, Nada A. Three-dimensional ultrasonography and power Doppler for discrimination between benign and malignant endometrium in premenopausal women with abnormal uterine bleeding. BMC WOMENS HEALTH 2016; 16:18. [PMID: 26980265 PMCID: PMC4793544 DOI: 10.1186/s12905-016-0297-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2015] [Accepted: 03/09/2016] [Indexed: 08/30/2023]
Abstract
BACKGROUND Ultrasonography has been extensively used in women suspected of having a gynecological malignancy. The aim of this study is to evaluate the efficacy of 3D ultrasonography and power Doppler for discrimination between benign and malignant endometrium in premenopausal women with abnormal uterine bleeding. METHODS This cross-sectional study included 78 premenopausal women with abnormal uterine bleeding scheduled for hysteroscopy and endometrial curettage. The endometrial thickness (ET), uterine artery pulsatility index (PI) and resistance index (RI), and endometrial volume (EV) and 3D power Doppler vascularization index (VI), flow index (FI), and vascularization flow index (VFI) were measured and compared with hysteroscopic and histopathologic findings. RESULTS The ET (P <0.001), EV (P <0.001), and endometrial VI (P <0.001) and VFI (P = 0.043) were significantly increased in patients with atypical endometrial hyperplasia and endometrial carcinoma (n = 10) than those with benign endometrium (n = 68); whereas, the uterine artery PI and RI and endometrial FI were not significantly different between the two groups. The best marker for discrimination between benign and malignant endometrium was the VI with an area under the ROC curve of 0.88 at a cutoff value of 0.81%. CONCLUSION 3D ultrasonography and power Doppler, especially endometrial VI, may be useful for discrimination between benign and malignant endometrium in premenopausal women with abnormal uterine bleeding.
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Affiliation(s)
- Mohamed El-Sharkawy
- Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt.
| | - Akmal El-Mazny
- Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Wafaa Ramadan
- Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Dina Hatem
- Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Aly Abdel-Hafiz
- Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Hammam
- Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Adel Nada
- Department of Obstetrics and Gynecology, Faculty of Medicine, Cairo University, Cairo, Egypt
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The association between codon72 polymorphism of p53 gene and the risk of endometrial cancer: an updating meta-analysis. Arch Gynecol Obstet 2016; 294:353-9. [DOI: 10.1007/s00404-015-4005-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2015] [Accepted: 12/22/2015] [Indexed: 12/22/2022]
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The rare presentation of sinus tarsi syndrome secondary to metastasis in a patient with endometrial carcinoma. Radiol Case Rep 2015; 6:414. [PMID: 27307895 PMCID: PMC4901158 DOI: 10.2484/rcr.v6i2.414] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022] Open
Abstract
Metastasis to bone or synovial tissue in the distal extremity is a rare event for endometrial carcinoma. This case report involves a 76-year-old female with stage II endometrial cancer who developed persistent ankle pain after a transabdominal hysterectomy and bilateral salpingo-oophorectomy. Plain films were initially negative. An MRI several weeks later demonstrated an abnormality in the synovial tissue of the sinus tarsi and in the distal tibia. A bone scan revealed increased activity on both sides of the ankle joint. Soft-tissue biopsy of the sinus tarsi was positive for endometrial adenocarcinoma. This is the first reported case of sinus tarsi syndrome, a chronic pain condition in the sinus tarsi of the hindfoot, secondary to metastatic endometrial carcinoma.
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Chen Q, Gao Q, Chen K, Wang Y, Chen L, Li XU. Curcumin suppresses migration and invasion of human endometrial carcinoma cells. Oncol Lett 2015; 10:1297-1302. [PMID: 26622667 DOI: 10.3892/ol.2015.3478] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2014] [Accepted: 05/12/2015] [Indexed: 01/08/2023] Open
Abstract
Curcumin, a widely used Chinese herbal medicine, has historically been used in anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism of curcumin in endometrial carcinoma (EC) are still poorly understood. The purpose of this study was to detect the anti-metastatic effects of curcumin and the associated mechanism(s) in EC. Based on assays carried out in EC cell lines, it was observed that curcumin inhibited EC cell migration and invasion in vitro. Furthermore, following treatment with curcumin for 24 h, there was a decrease in the expression levels of matrix metalloproteinase (MMP)-2 and -9 as well as proteinase activity in EC cells. Moreover, curcumin treatment significantly decreased the levels of the phosphorylated form of extracellular signal-regulated kinase (ERK) 1/2. MEK1 overexpression partially blocked the anti-metastatic effects of curcumin. Combined treatment with ERK inhibitor U0126 and curcumin resulted in a synergistic reduction in MMP-2/-9 expression; the invasive capabilities of HEC-1B cells were also inhibited. In conclusion, curcumin inhibits tumor cell migration and invasion by reducing the expression and activity of MMP-2/9 via the suppression of the ERK signaling pathway, suggesting that curcumin is a potential therapeutic agent for EC.
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Affiliation(s)
- Qian Chen
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Qing Gao
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Kunlun Chen
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Yidong Wang
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - Lijuan Chen
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, P.R. China
| | - X U Li
- Center for Translational Medicine, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
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Stewart CJR, Crook ML. Fascin expression in undifferentiated and dedifferentiated endometrial carcinoma. Hum Pathol 2015; 46:1514-20. [PMID: 26239622 DOI: 10.1016/j.humpath.2015.06.011] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/16/2015] [Revised: 06/04/2015] [Accepted: 06/10/2015] [Indexed: 12/24/2022]
Abstract
The actin-binding protein fascin promotes cellular invasion, and increased fascin expression correlates with adverse prognostic factors in a variety of tumors. Fascin up-regulation may also be associated with epithelial-mesenchymal transition in neoplastic epithelial cells. This study investigated fascin expression in undifferentiated and dedifferentiated endometrial carcinoma (UEC), a clinically aggressive variant of endometrial neoplasia. Twenty-two UECs, 5 of which were entirely undifferentiated and 17 dedifferentiated, were examined. In the dedifferentiated group, staining was compared between the differentiated and undifferentiated tumor components. Where applicable, fascin expression was noted in foci of lymphovascular space invasion. The mean age was 67.6 years, and 11 patients (50%) presented with stage III or IV disease. The undifferentiated tumor component showed diffuse fascin expression in 20 cases (91%) including 4 of 5 pure undifferentiated carcinomas and 16 of 17 dedifferentiated carcinomas. In contrast, the low-grade endometrioid carcinoma component of 13 (77%) of 17 dedifferentiated carcinomas was fascin negative or showed only focal staining. Intravascular undifferentiated tumor cells were identified in 16 cases, and these were consistently fascin positive, whereas low-grade intravascular tumor cells, present in 2 cases, were not stained. Fascin up-regulation may be a contributory factor toward the highly invasive character of UEC and could represent an epithelial-mesenchymal transition-like process in these tumors. Fascin expression in intravascular tumor cells may be permissive toward intravascular survival and metastatic risk.
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Affiliation(s)
- Colin J R Stewart
- Department of Histopathology, King Edward Memorial Hospital, Perth, Western Australia 6008, Australia; School for Women's and Infants' Health, University of Western Australia, Perth, Western Australia 6008, Australia.
| | - Maxine L Crook
- Department of Histopathology, King Edward Memorial Hospital, Perth, Western Australia 6008, Australia
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NICULA RENATA, COSTIN NICOLAE. Management of endometrial modifications in perimenopausal women. CLUJUL MEDICAL (1957) 2015; 88:101-10. [PMID: 26528056 PMCID: PMC4576794 DOI: 10.15386/cjmed-421] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 02/27/2015] [Accepted: 03/16/2015] [Indexed: 11/30/2022]
Abstract
Perimenopause has a variable length and time of onset and is characterized by its variability in hormonal levels. The histological changes in the perimenopausal endometrium may be represented by nonproliferative or proliferative benign or malignant lesions. A commonly encountered manifestation of endometrium lesions during menopausal transition is the abnormal uterine bleeding (AUB). The clinical management of AUB must follow a standardized classification system for optimal results. The medical and surgical treatment must be adapted according to age, risk factors, symptoms, and cycle irregularities. Use of alternative therapies and proper diet may result in improved long-term outcomes.
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Affiliation(s)
- RENATA NICULA
- Dominic Stanca Clinic of Obstetrics and Gynecology, Cluj-Napoca, RomaniaIuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
| | - NICOLAE COSTIN
- Dominic Stanca Clinic of Obstetrics and Gynecology, Cluj-Napoca, RomaniaIuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania
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Yamamoto T, Mori T, Sawada M, Matsushima H, Ito F, Akiyama M, Kitawaki J. Loss of AF-6/afadin induces cell invasion, suppresses the formation of glandular structures and might be a predictive marker of resistance to chemotherapy in endometrial cancer. BMC Cancer 2015; 15:275. [PMID: 25879875 PMCID: PMC4399104 DOI: 10.1186/s12885-015-1286-x] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/25/2014] [Accepted: 03/30/2015] [Indexed: 02/04/2023] Open
Abstract
Background AF-6/afadin plays an important role in the formation of adherence junctions. In breast and colon cancer, loss of AF-6/afadin induces cell migration and cell invasion. We aimed to elucidate the role of AF-6/afadin in human endometrial cancer. Methods Morphology and AF-6/afadin expression in endometrial cancer cell lines was investigated by 3-dimensional culture. We used Matrigel invasion assay to demonstrate AF-6/afadin knockdown induced invasive capability. Cell proliferation assay was performed to estimate chemoresistance to doxorubicin, paclitaxel and cisplatin induced by AF-6/afadin knockdown. The associations between AF-6/afadin expression and clinicopathological status were determined by immunohistochemical analysis in endometrial cancer tissues. Informed consent was obtained from all patients before the study. Results The majority of cell clumps in 3-dimensional cultures of Ishikawa cells that strongly expressed AF-6/afadin showed round gland-like structures. In contrast, the cell clumps in 3-dimensional cultures of HEC1A and AN3CA cells—both weakly expressing AF-6/afadin—showed irregular gland-like structures and disorganized colonies with no gland-like structures, respectively. AF-6/afadin knockdown resulted in reduced number of gland-like structures in 3-dimensional cultures and enhancement of cell invasion and phosphorylation of ERK1/2 and Src in the highly AF-6/afadin-expressing endometrial cancer cell line. Inhibitors of MAPK/ERK kinase (MEK) (U0126) and Src (SU6656) suppressed the AF-6/afadin knockdown-induced invasive capability. AF-6/afadin knockdown induced chemoresistance to doxorubicin, paclitaxel and cisplatin in Ishikawa cells, not in HEC1A. Immunohistochemical analysis showed that AF-6/afadin expression was significantly associated with myometrial invasion and high histological grade. Conclusions AF-6/afadin regulates cell morphology and invasiveness. Invasive capability is partly regulated through the ERK and Src pathway. The inhibitors to these pathways might be molecular-targeted drugs which suppress myometrial invasion in endometrial cancer. AF-6/afadin could be a useful selection marker for fertility-sparing therapy for patients with atypical hyperplasia or grade 1 endometrioid adenocarcinoma with no myometrial invasion. AF-6/afadin knockdown induced chemoresistance especially to cisplatin. Therefore, loss of AF-6/afadin might be a predictive marker of chemoresistance to cisplatin.
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Affiliation(s)
- Takuro Yamamoto
- Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
| | - Taisuke Mori
- Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
| | - Morio Sawada
- Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
| | - Hiroshi Matsushima
- Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
| | - Fumitake Ito
- Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
| | - Makoto Akiyama
- Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
| | - Jo Kitawaki
- Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.
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Wittenberger T, Sleigh S, Reisel D, Zikan M, Wahl B, Alunni-Fabbroni M, Jones A, Evans I, Koch J, Paprotka T, Lempiäinen H, Rujan T, Rack B, Cibula D, Widschwendter M. DNA methylation markers for early detection of women's cancer: promise and challenges. Epigenomics 2015; 6:311-27. [PMID: 25111485 DOI: 10.2217/epi.14.20] [Citation(s) in RCA: 64] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
Breast, ovarian and endometrial cancers cause significant morbidity and mortality. Despite the presence of existing screening, diagnostic and treatment modalities, they continue to pose considerable unsolved challenges. Overdiagnosis is a growing problem in breast cancer screening and neither screening nor early diagnosis of ovarian or endometrial cancer is currently possible. Moreover, treatment of the diversity of these cancers presenting in the clinic is not sufficiently personalized at present. Recent technological advances, including reduced representation bisulfite sequencing, methylation arrays, digital PCR, next-generation sequencing and advanced statistical data analysis, enable the analysis of methylation patterns in cell-free tumor DNA in serum/plasma. Ongoing work is bringing these methods together for the analysis of samples from large clinical trials, which have been collected well in advance of cancer diagnosis. These efforts pave the way for the development of a noninvasive method that would enable us to overcome existing challenges to personalized medicine.
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Myriokefalitaki E, Vorgias G, Vlahos G, Rodolakis A. Prognostic value of preoperative Ca125 and Tag72 serum levels and their correlation to disease relapse and survival in endometrial cancer. Arch Gynecol Obstet 2015; 292:647-54. [DOI: 10.1007/s00404-015-3675-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2014] [Accepted: 02/17/2015] [Indexed: 10/23/2022]
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Sianou A, Galyfos G, Moragianni D, Andromidas P, Kaparos G, Baka S, Kouskouni E. The role of microRNAs in the pathogenesis of endometrial cancer: a systematic review. Arch Gynecol Obstet 2015; 292:271-82. [PMID: 25697925 DOI: 10.1007/s00404-015-3660-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2014] [Accepted: 02/09/2015] [Indexed: 02/06/2023]
Abstract
INTRODUCTION Epigenetics seem to play a primary role in the current research on the pathogenesis of different types of endometrial cancer. Data so far indicate that microRNAs regulate different pathways that could lead to carcinogenesis when not functioning properly. The aim of this review is to summarize current knowledge on microRNAs that have been associated with endometrial cancer development. MATERIAL AND METHODS From July 2014 to August 2014, we conducted a comprehensive research utilizing major online search engines (Pubmed, Crossref, Google Scholar). The main keywords used in our search were endometrial cancer/carcinoma; microRNA; epigenetics; novel biomarkers; pathogenesis. RESULTS Overall, we identified 155 studies, although only 77 were eligible for this review. Different miRNAs were identified to contribute either promoting the carcinogenesis in the endometrium or inhibiting different steps of endometrial cancer development. Tumour growth, cell proliferation, apoptosis and invasion metastasis have been identified as the main processes where miRNAs seem to be implicated. CONCLUSIONS microRNAs are effective regulators of gene expression that has a significant role in the pathogenesis of endometrial cancer. Research concerning possible therapeutic implications has been promising, although there is still a significant distance to be covered between research observations and clinical results. Extensive preclinical and translational research is still required to improve the efficacy and minimize unwanted effects of miRNAs-based therapy.
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Affiliation(s)
- Argiri Sianou
- Department of Microbiology, Areteion Hospital, University of Athens Medical School, Athens, Greece,
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Adiponectin mediates antiproliferative and apoptotic responses in endometrial carcinoma by the AdipoRs/AMPK pathway. Gynecol Oncol 2015; 137:311-20. [PMID: 25703675 DOI: 10.1016/j.ygyno.2015.02.012] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 02/09/2015] [Indexed: 01/21/2023]
Abstract
OBJECTIVE Determine the serum adiponectin levels in endometrial carcinoma (EC) cases and controls and explore the correlation between them. We assessed the functions of AdipoR1 and AdipoR2 in endometrial cancer cells to determine whether the AMPK/ERK and Akt pathways mediate the effects of adiponectin-induced apoptosis and anti-proliferation. MATERIAL AND METHODS The serum adiponectin levels were measured via enzyme-linked immunosorbent assay (ELISA). The proliferation and apoptosis rates were determined with MTT and annexin V/PI assays. To evaluate the activation of AMPK, ERK, and Akt and the expression of Bcl-2 and Cyclin D1, western blot analysis was performed in Ishikawa 3-H-12 cells. We down-regulated AdipoRs by si-RNA to assess their functions. RESULTS The serum adiponectin levels were significantly decreased in patients with EC compared to controls. The adiponectin-induced apoptosis and anti-proliferation effects in EC cells were blocked by Compound C. Ishikawa 3-H-12 cells exhibited time- and dose-dependent increases in the p-AMPK levels after treatment with adiponectin. Adiponectin treatment reduced the levels of ERK and Akt phosphorylations and cyclin D1 and Bcl-2 mRNA and protein expression. Compound C blocked the effects on ERK, Akt, cyclin D1, and Bcl-2. AdipoR1 and AdipoR2 were involved in adiponectin-induced growth inhibition and ERK activation inhibition. We speculated that AdipoR1 has a greater role than adipoR2 in apoptosis and Akt activation inhibition after adiponectin treatment. CONCLUSION Adiponectin was an apoptotic and anti-proliferation agent for EC cells, and these effects were dependent on the AMPK/ERK and Akt pathways. AdipoR1 and AdipoR2 may play different roles in this process.
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50
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Significant association between IL-32 gene polymorphisms and susceptibility to endometrial cancer in Chinese Han women. Tumour Biol 2015; 36:5265-72. [PMID: 25663496 DOI: 10.1007/s13277-015-3186-8] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2014] [Accepted: 01/27/2015] [Indexed: 01/27/2023] Open
Abstract
Interleukin-32 (IL-32), a pro-inflammatory chemokine, has been reported to be involved in inflammatory, infectious diseases and even cancers. This study aimed to investigate whether two genetic variants (rs28372698 and rs12934561) of IL-32 were associated with susceptibility to endometrial cancer (EC) in Chinese Han women by a hospital-based study with 272 EC patients and 337 healthy controls. Our results showed that the frequencies of TT genotype (P = 0.012, OR = 2.37, 95 % CI = 1.32-4.28) and T allele (P = 0.026, OR = 1.320, 95 % CI = 1.036-1.681) of rs28372698 in EC patients were significantly higher than controls. Clinical analyses indicated the TT genotype frequency was relevant to high clinical stage and cervical invasion. Furthermore, the frequencies of CC genotype (P = 0.0077, OR = 1.62, 95 % CI = 1.05-2.50) and C allele (P = 0.043, OR = 1.269, 95 % CI = 1.011-1.592) of rs12934561 were also significantly higher in EC patients than controls. Stratification analyses revealed that CC genotype was more frequent in endometrioid adenocarcinoma or EC without parametrial invasion. This study demonstrates that IL-32 gene polymorphisms are significantly associated with increased EC susceptibility in Chinese Han women.
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