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Sullivan MW, Chui MH, Selenica P, Long Roche K, Sonoda Y, Grisham RN, Kyi C, Momeni-Boroujeni A, Abu-Rustum NR, Weigelt B, O'Cearbhaill RE. Anaplastic carcinoma of the ovary: A single-institution experience and molecular analysis. Gynecol Oncol 2025; 195:144-148. [PMID: 40112666 PMCID: PMC12010851 DOI: 10.1016/j.ygyno.2025.03.021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2025] [Revised: 02/26/2025] [Accepted: 03/12/2025] [Indexed: 03/22/2025]
Abstract
OBJECTIVE We describe a tertiary referral center's experience with anaplastic ovarian carcinoma and characterize the genetic landscape of these rare tumors. METHODS Anaplastic ovarian carcinomas were retrospectively identified from institutional databases from 2013 to 2023. Clinical data and survival outcomes were abstracted from the electronic medical record. Molecular data were obtained from clinical tumor-normal panel sequencing. RESULTS Thirteen tumors were identified; 12 (92 %) were associated with or arose from a mucinous carcinoma, and 6 (46 %) were found in a mural nodule. Median age at diagnosis was 39 years (range, 19-77); 6 patients had stage I disease (3 stage IA), 1 had stage II, 5 had stage III, and 1 had stage IV. All patients underwent surgery. First-line postoperative therapy included carboplatin-paclitaxel doublet (n = 8), a 5-fluorouracil-oxaliplatin-based regimen (FOLFOX, n = 1; XELOX, n = 2), and ifosfamide/paclitaxel (n = 1). Two patients did not receive adjuvant chemotherapy for early-stage disease. Six patients had progression or recurrence; 5 had platinum-refractory disease and 1 had an initial progression-free interval of 6.8 months. For the 7 patients without recurrence, median follow-up was 79.7 months. Median overall survival for all patients was 28.1 months (range, 7.8-139.2). Five patients died of their disease. Ten patients had clinical panel sequencing, revealing recurrent somatic KRAS G12D/V hotspot mutations (8 of 10, 80 %) and genetic alterations affecting cell cycle-related genes, including TP53 (6 of 10, 60 %) and CDKN2A (6 of 10, 60 %). CONCLUSIONS Anaplastic ovarian carcinoma is characterized by KRAS, TP53, and CDKN2A alterations. Novel treatment approaches are needed due to the high rate of platinum-refractory disease.
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Affiliation(s)
- Mackenzie W Sullivan
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - M Herman Chui
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Pier Selenica
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Kara Long Roche
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA
| | - Yukio Sonoda
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA
| | - Rachel N Grisham
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA
| | - Chrisann Kyi
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA
| | - Amir Momeni-Boroujeni
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Nadeem R Abu-Rustum
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Obstetrics and Gynecology, Weill Cornell Medical College, New York, NY, USA
| | - Britta Weigelt
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Roisin E O'Cearbhaill
- Gynecologic Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, USA.
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Köbel M, Parra-Herran C, Gorringe K. Diagnosis and Risk Stratification of Ovarian Mucinous Neoplasms: Pattern of Invasion, Immunohistochemistry, and Molecular Diagnostics. Adv Anat Pathol 2025; 32:85-97. [PMID: 39523705 DOI: 10.1097/pap.0000000000000473] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2024]
Abstract
Ovarian mucinous tumors are subclassified in multiple categories. Recent studies have highlighted issues in interobserver reproducibility. This review will focus on some new developments including criteria and ancillary tests that may help to improve interobserver reproducibility at clinically important thresholds. These issues include proposals for a separate terminology of teratoma-associated ovarian mucinous neoplasms, the role of TP53 immunohistochemistry in distinction of crowded mucinous borderline tumors and expansile mucinous carcinomas as well as the assignment of the infiltrative pattern of invasion, which recently has been validated as important prognostic factor even in low stage mucinous ovarian carcinoma.
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Affiliation(s)
- Martin Köbel
- Department of Pathology, University of Calgary, Alberta, Canada
| | - Carlos Parra-Herran
- Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA
| | - Kylie Gorringe
- Sir Peter MacCallum Department of Oncology, The University of Melbourne
- Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
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Li J, Huang H, Zeng Q, Chen X, Chen L. Case report: Ovarian mucinous tumor with a mural nodule of liposarcoma: a rare case. Front Oncol 2024; 14:1436854. [PMID: 39220649 PMCID: PMC11361924 DOI: 10.3389/fonc.2024.1436854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Accepted: 07/25/2024] [Indexed: 09/04/2024] Open
Abstract
Background Ovarian mucinous tumor with a mural nodule is a rare and special type of ovarian surface epithelial-stromal tumor. Mural nodules are morphologically classified into three types: sarcoma-like, anaplastic carcinomatous, and true sarcomatous nodules. Ovarian mucinous tumors with true sarcomatous mural nodules are rare and challenging to diagnose, with only 10 cases reported worldwide. Currently, liposarcoma mural nodules remain unreported. Case presentation A 91-year-old woman was hospitalized for postmenopausal vaginal bleeding for 3 weeks. Imaging revealed a large cystic mass (20.0 cm × 17.7 cm × 12.8 cm) on the right ovary. The mass was multilocular cystic, with a mural nodule (1.4 cm × 1.2 cm × 1.0 cm) in the focal cyst wall. Based on histological morphology, immunohistochemical staining, and MDM2/CDK4 fluorescence in situ hybridization testing, the diagnosis was ovarian mucinous cystadenoma with a mural nodule of well-differentiated liposarcoma. To the best of our knowledge, this has never been reported before. High-throughput sequencing identified KRAS mutations in the ovarian mucinous cystadenoma. However, the liposarcoma mural nodule did not exhibit KRAS mutations but displayed copy number amplifications of CDK4 and DDR2, as well as a frameshift mutation in exon 13 of ASXL1 (p. A627Gfs*8). Conclusions This case broadens the morphological spectrum of mural nodules in ovarian mucinous tumors, deepening our knowledge of this rare morphology. Meanwhile, through high-throughput sequencing, we found no overlapping genetic evidence between the liposarcoma mural nodule and associated ovarian mucinous cystadenoma.
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Affiliation(s)
- Jiezhen Li
- Provincial Clinical Medical College of Fujian Medical University, Department of Pathology, Fujian Provincial Hospital, Fuzhou, China
| | - Haijian Huang
- Provincial Clinical Medical College of Fujian Medical University, Department of Pathology, Fujian Provincial Hospital, Fuzhou, China
| | - Qiang Zeng
- First Affiliated Hospital of Fujian Medical University, Department of Pathology, Fuzhou, China
| | - Xin Chen
- Provincial Clinical Medical College of Fujian Medical University, Department of Pathology, Fujian Provincial Hospital, Fuzhou, China
| | - Lingfeng Chen
- Provincial Clinical Medical College of Fujian Medical University, Department of Pathology, Fujian Provincial Hospital, Fuzhou, China
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Li S, Zhu J, Jiang N, Guo Y, Hou M, Liu X, Yang J, Yang X. Recurrent mucinous carcinoma with sarcomatoid and sarcomatous mural nodules: a case report and literature review. Front Oncol 2024; 14:1387700. [PMID: 38903727 PMCID: PMC11187075 DOI: 10.3389/fonc.2024.1387700] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2024] [Accepted: 05/17/2024] [Indexed: 06/22/2024] Open
Abstract
Ovarian mucinous tumors with sarcomatous mural nodules are rare. Sarcomatous nodules have a bad prognosis. Its diagnosis and treatment are controversial.It is still controversial whether malignant mural nodules represent a dedifferentiated form of mucinous tumors or collisional tumors. This is a case report of a 32-year-old female diagnosed with ovarian mucinous tumor recurred as a mucinous carcinoma combined with sarcomatoid and undifferentiated sarcoma mural nodules after surgery and chemotherapy. The primary lesion did not have a sarcomatous component after comprehensive sampling and repeated review, while the recurrent lesion had a predominantly sarcomatous component. The patient received a second operation and postoperative chemotherapy plus Anlotinib with no progression at 16 months of follow-up. Primary mucinous carcinoma and sarcomatous mural nodules revealed the same K-RAS mutation(c.35G>T, pG12V), TP53 mutation (c.817C>T, p.R273C), MLL2 mutation(c.13450C>T, p.R4484) and NF1 mutation(c.7876A>G, p.S2626G). We present a comprehensive analysis on morphologic characteristics, molecular detection results, clinical management, and prognosis of ovarian mucinous tumors with mural nodules of sarcomatoid and undifferentiated sarcoma. Mutation sharing between primary mucinous carcinoma and recurrent sarcomatous nodules supports monoclonal origin of primary and recurrent tumors, suggesting a tendency for sarcomatous differentiation during the progression of epithelial tumors. Malignant mural nodules represent dedifferentiation in mucinous ovarian tumors rather than collision of two different tumor types. Therefore, it is imperative to conduct comprehensive sampling, rigorous clinical examination, and postoperative follow-up in order to thoroughly evaluate all mural nodules of ovarian mucinous tumors due to their potential for malignancy and sarcomatous differentiation.
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Affiliation(s)
- Simin Li
- Department of Gynecology and Obstetrics, First Affiliated Hospital of Xi ‘an Jiaotong University, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Jingyu Zhu
- Department of Gynecology and Obstetrics, First Affiliated Hospital of Xi ‘an Jiaotong University, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Na Jiang
- Department of Pathology, First Affiliated Hospital of Xi ‘an Jiaotong University, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Yanping Guo
- Department of Gynecology and Obstetrics, First Affiliated Hospital of Xi ‘an Jiaotong University, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Meng Hou
- Department of Gynecology and Obstetrics, First Affiliated Hospital of Xi ‘an Jiaotong University, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xi Liu
- Department of Pathology, First Affiliated Hospital of Xi ‘an Jiaotong University, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Jin Yang
- Department of Oncology, First Affiliated Hospital of Xi ‘an Jiaotong University, Xi’an Jiaotong University, Xi’an, Shaanxi, China
| | - Xiaofeng Yang
- Department of Gynecology and Obstetrics, First Affiliated Hospital of Xi ‘an Jiaotong University, Xi’an Jiaotong University, Xi’an, Shaanxi, China
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Feng Y. An integrated machine learning-based model for joint diagnosis of ovarian cancer with multiple test indicators. J Ovarian Res 2024; 17:45. [PMID: 38378582 PMCID: PMC10877874 DOI: 10.1186/s13048-024-01365-9] [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: 08/31/2023] [Accepted: 02/01/2024] [Indexed: 02/22/2024] Open
Abstract
OBJECTIVE To construct a machine learning diagnostic model integrating feature dimensionality reduction techniques and artificial neural network classifiers to develop the value of clinical routine blood indexes for the auxiliary diagnosis of ovarian cancer. METHODS Patients with ovarian cancer clearly diagnosed in our hospital were collected as a case group (n = 185), and three groups of patients with other malignant otolaryngology tumors (n = 138), patients with benign otolaryngology diseases (n = 339) and those with normal physical examination (n = 92) were used as an overall control group. In this paper, a fully automated segmentation network for magnetic resonance images of ovarian cancer is proposed to improve the reproducibility of tumor segmentation results while effectively reducing the burden on radiologists. A pre-trained Res Net50 is used to the three edge output modules are fused to obtain the final segmentation results. The segmentation results of the proposed network architecture are compared with the segmentation results of the U-net based network architecture and the effect of different loss functions and region of interest sizes on the segmentation performance of the proposed network is analyzed. RESULTS The average Dice similarity coefficient, average sensitivity, average specificity (specificity) and average hausdorff distance of the proposed network segmentation results reached 83.62%, 89.11%, 96.37% and 8.50, respectively, which were better than the U-net based segmentation method. For ROIs containing tumor tissue, the smaller the size, the better the segmentation effect. Several loss functions do not differ much. The area under the ROC curve of the machine learning diagnostic model reached 0.948, with a sensitivity of 91.9% and a specificity of 86.9%, and its diagnostic efficacy was significantly better than that of the traditional way of detecting CA125 alone. The model was able to accurately diagnose ovarian cancer of different disease stages and showed certain discriminative ability for ovarian cancer in all three control subgroups. CONCLUSION Using machine learning to integrate multiple conventional test indicators can effectively improve the diagnostic efficacy of ovarian cancer, which provides a new idea for the intelligent auxiliary diagnosis of ovarian cancer.
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Affiliation(s)
- Yiwen Feng
- Departments of Obstetrics and Gynecology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200080, P.R. China.
- Jiuquan Hospital, Shanghai General Hospital, 200003, Shanghai, China.
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Hernandez Acevedo PI, Carter GJ, Courtney-Brooks M, Clark BZ. Ovarian serous borderline tumor with mural nodules of anaplastic carcinoma and omental involvement: A case report. Rare Tumors 2023; 15:20363613231172260. [PMID: 37113477 PMCID: PMC10126381 DOI: 10.1177/20363613231172260] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 04/10/2023] [Indexed: 04/29/2023] Open
Abstract
Mural nodules are rarely identified in cystic ovarian neoplasms, and have been categorized into sarcoma-like, sarcomatous, and anaplastic carcinomatous types. Most reports of these mural nodules have been described in mucinous ovarian tumors. In this case report, we describe an ovarian serous borderline tumor with mural nodules composed of high-grade carcinoma with anaplastic features and necrosis, including the morphologic features, immunoprofile, and results of tumor DNA sequencing. Omental involvement was also identified. Recognition of this phenomenon in serous tumors is important, so that thickened areas of cyst wall in ovarian serous tumors will be thoroughly examined.
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Affiliation(s)
| | - Gloria J Carter
- Division of Breast and Gynecologic Pathology, University of Pittsburgh Medical Center, Magee-Womens Hospital, Pittsburgh, PA, USA
| | - Madeleine Courtney-Brooks
- Division of Gynecologic Oncology, University of Pittsburgh Medical Center, Magee-Womens Hospital, Pittsburgh, PA, USA
| | - Beth Z Clark
- Division of Breast and Gynecologic Pathology, University of Pittsburgh Medical Center, Magee-Womens Hospital, Pittsburgh, PA, USA
- Beth Z Clark, Division of Breast and Gynecologic Pathology, Department of Pathology, University of Pittsburgh Medical Center, Magee-Womens Hospital, Pittsburgh, PA, USA
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7
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Rapid recurrence of a ruptured mucinous borderline ovarian tumor harboring K-RAS mutation followed by progression into anaplastic carcinoma with TP53 mutation. Heliyon 2022; 8:e10877. [PMID: 36281401 PMCID: PMC9586857 DOI: 10.1016/j.heliyon.2022.e10877] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 08/13/2022] [Accepted: 09/28/2022] [Indexed: 11/06/2022] Open
Abstract
We describe the case of a young patient with a borderline mucinous ovarian tumor that progressed into ipsilateral ovarian anaplastic carcinoma in only 3 months with metastasis to the contralateral ovary and extensive spread in the pelvic and abdominal regions. The mucinous tumor harbored micro-foci of intraepithelial carcinoma, but no mural nodules, microinvasion, or invasive adenocarcinoma were detected. Notably, a rupture on the ovarian mass and low-grade pseudomyxoma peritonei were present. Next-generation sequencing identified an identical KRAS mutation in the mucinous tumor and anaplastic carcinoma, while the latter had KRAS gene amplification and CDKN2A, MPL and TP53 mutations. These findings indicate the anaplastic carcinoma might have arisen via recurrence, malignant transformation and dedifferentiation of the former low-grade mucinous tumor. We consider that the mass rupture and pseudomyxoma peritonei were high-risk factors for recurrence, while genetic mutations were key drivers of progression. Accordingly, such cases may benefit from active surgical treatment and early chemotherapy.
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8
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Invasive Mucinous Adenocarcinoma of the Lung with a Mural Nodule-like Lesion. Am J Surg Pathol 2022; 46:1524-1532. [PMID: 35939825 DOI: 10.1097/pas.0000000000001938] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Invasive mucinous adenocarcinoma (IMA) of the lung shares some clinicopathological features with mucinous carcinoma of other organs, such as the ovary. Sarcoma-like lesions, called mural nodules, have been reported in the cystic walls of ovarian mucinous tumors. In this study, we analyzed 213 surgically resected cases of IMA of the lung to determine whether similar mural nodule-like lesions were present. We considered abrupt discrete lesions composed of dedifferentiated tumor cells as mural nodule-like lesions. Of 213 IMAs, we identified 11 tumors with mural nodule-like lesions that were histologically categorized into three subtypes similar to those in the ovary. The sarcomatoid and anaplastic carcinoma-like nodules were composed of spindle cell proliferations and polygonal undifferentiated carcinoma, respectively. Sarcoma-like lesions mimicked sarcomatoid nodules, but the spindle cell proliferations were considered a fibroblastic reaction to the scattered, isolated clusters of tumor cells. Molecular analysis of the components of differentiated IMAs and mural nodule-like lesions revealed a clonal relationship, suggesting a spectrum of tumors with different histology. Clinicopathologically, an older age, the male sex, and smokers were significantly associated with IMAs with mural nodule-like lesions. Notably, patient outcomes were unaffected by the presence or absence of these lesions. Our findings demonstrated that IMA of the lung rarely develops mural nodule-like lesions (11 of 213, 5%). Despite a histological impression of clinical aggressiveness, there was no clear trend in patient outcomes, suggesting that pathologists should avoid overstating this mural nodule-like lesion.
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Wang XJ, Wang CY, Xi YF, Bu P, Wang P. Ovarian mucinous tumor with mural nodules of anaplastic carcinoma: Three case reports. World J Clin Cases 2022; 10:7459-7466. [PMID: 36158006 PMCID: PMC9353926 DOI: 10.12998/wjcc.v10.i21.7459] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2021] [Revised: 01/08/2022] [Accepted: 06/03/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Anaplastic carcinoma mural nodules in ovarian mucinous tumors are very rare. This study aimed to report the morphological characteristics, molecular detection results, clinical treatment and prognosis of three ovarian mucinous tumors with mural nodules of anaplastic carcinoma.
CASE SUMMARY The pathomorphological features, molecular detection results, clinical treatment and prognosis of anaplastic carcinoma mural nodules were described in three cases. In case 1, sarcoma-like mural nodules (SLMNs) coexisted with anaplastic carcinoma mural nodules. No mutation was found in mucinous tumors. KRAS mutation was found in anaplastic carcinoma nodules and heterotypic cells were found in SLMNs. In case 2, KRAS mutation occurred in the mucinous epithelium and BRAF mutation occurred in mural nodules. In case 3, both mural nodules and mucinous tumors had the same KRAS mutation and a morphological transition between them was observed. All three patients died within 2 years, whether receiving chemotherapy or not.
CONCLUSION Anaplastic carcinoma mural nodules may develop from dedifferentiation of mucinous tumors or are unrelated to mucinous tumors.
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Affiliation(s)
- Xiao-Juan Wang
- Department of Pathology, Shanxi Cancer Hospital and Institute, Taiyuan 030013, Shanxi Province, China
| | - Chun-Yan Wang
- Department of Molecular Biology, Department of Blood Transfusion, Shanxi Cancer Hospital and Institute, Taiyuan 030013, Shanxi Province, China
| | - Yan-Feng Xi
- Department of Pathology, Shanxi Cancer Hospital and Institute, Taiyuan 030013, Shanxi Province, China
| | - Peng Bu
- Department of Pathology, Shanxi Cancer Hospital and Institute, Taiyuan 030013, Shanxi Province, China
| | - Pei Wang
- Department of Gynecology, Shanxi Cancer Hospital and Institute, Taiyuan 030013, Shanxi Province, China
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Wang CY, Wang P, Wang XJ, Wang XY. Sessile serrated adenoma of the appendix coexists with anaplastic carcinoma mural nodules originating from ovarian mucinous tumors: A case report. Niger J Clin Pract 2022; 25:964-966. [DOI: 10.4103/njcp.njcp_1782_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
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Youssef A, Haskali MB, Gorringe KL. The Protein Landscape of Mucinous Ovarian Cancer: Towards a Theranostic. Cancers (Basel) 2021; 13:5596. [PMID: 34830751 PMCID: PMC8616050 DOI: 10.3390/cancers13225596] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Revised: 11/02/2021] [Accepted: 11/03/2021] [Indexed: 01/20/2023] Open
Abstract
MOC is a rare histotype of epithelial ovarian cancer, and current management options are inadequate for the treatment of late stage or recurrent disease. A shift towards personalised medicines in ovarian cancer is being observed, with trials targeting specific molecular pathways, however, MOC lags due to its rarity. Theranostics is a rapidly evolving category of personalised medicine, encompassing both a diagnostic and therapeutic approach by recognising targets that are expressed highly in tumour tissue in order to deliver a therapeutic payload. The present review evaluates the protein landscape of MOC in recent immunohistochemical- and proteomic-based research, aiming to identify potential candidates for theranostic application. Fourteen proteins were selected based on cell membrane localisation: HER2, EGFR, FOLR1, RAC1, GPR158, CEACAM6, MUC16, PD-L1, NHE1, CEACAM5, MUC1, ACE2, GP2, and PTPRH. Optimal proteins to target using theranostic agents must exhibit high membrane expression on cancerous tissue with low expression on healthy tissue to afford improved disease outcomes with minimal off-target effects and toxicities. We provide guidelines to consider in the selection of a theranostic target for MOC and suggest future directions in evaluating the results of this review.
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Affiliation(s)
- Arkan Youssef
- Department of Medicine, The University of Melbourne, Melbourne, VIC 3000, Australia;
| | - Mohammad B. Haskali
- The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC 3000, Australia;
- Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
| | - Kylie L. Gorringe
- The Sir Peter MacCallum Department of Oncology, The University of Melbourne, Melbourne, VIC 3000, Australia;
- Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
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Talia KL, Parra-Herran C, McCluggage WG. Ovarian mucinous and seromucinous neoplasms: problematic aspects and modern diagnostic approach. Histopathology 2021; 80:255-278. [PMID: 33963606 DOI: 10.1111/his.14399] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
The morphological spectrum of primary ovarian mucinous and seromucinous tumours is broad and presents an array of diagnostic challenges, many unique to these tumour types. This reflects the heterogeneous nature of these lesions, their varied histogenesis and evolving classification systems over recent decades, with further modification to the seromucinous category incorporated in the recently published 5th edition of the WHO Classification of Female Genital Tumours. In this review we provide an update on the classification of these neoplasms and discuss their histogenesis and diverse morphology, focusing on areas which are diagnostically problematic. We also cover tumour grading, differential diagnosis, immunohistochemistry, the recent elucidation of the molecular underpinnings of ovarian mucinous neoplasia and discuss the gross and intraoperative handling of these tumours. A number of diagnostic issues remain unresolved highlighting the importance of further research on this front, as well as a multidisciplinary approach in the care of patients with ovarian mucinous and seromucinous neoplasia.
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Affiliation(s)
- Karen L Talia
- Department of Pathology, Royal Women's Hospital and VCS Foundation, Melbourne, Australia
| | | | - W Glenn McCluggage
- Department of Pathology, Belfast Health and Social Care Trust, Belfast, United Kingdom
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