Patterns of clinicopathological features and outcome in epithelial ovarian cancer patients: 35 years of prospectively collected data

Irodi, Aparna; Rye, Tzyvia; Herbert, Karl E.; Churchman, Michael; Bartos, Clare; Mackean, Melanie; Nussey, Fiona; Herrington, C. Simon; Gourley, Charlie; Hollis, Robert L.

doi:10.1111/1471-0528.16264

Cited by 32 publications

(37 citation statements)

References 64 publications

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“…Clinical data. Baseline characteristics and outcome data were extracted from the Edinburgh Ovarian Cancer Database, wherein the diagnostic, treatment and follow-up data for every ovarian cancer patient treated at the Edinburgh Cancer Centre is prospectively entered as a part of routine care 5 . DSS was calculated from the date of pathologically confirmed OC diagnosis.…”

Section: Methodsmentioning

confidence: 99%

“…varian carcinomas (OC) are a heterogeneous group of malignancies comprising five core histological types, each with distinct pathological characteristics, molecular landscapes and clinical behaviour 1,2 . Endometrioid OC (EnOC) accounts for approximately 10% of all OC, with the majority of cases diagnosed as low grade, early stage disease with excellent clinical outcome [3][4][5] .…”

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confidence: 99%

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Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome

et al. 2020

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Endometrioid ovarian carcinoma (EnOC) demonstrates substantial clinical and molecular heterogeneity. Here, we report whole exome sequencing of 112 EnOC cases following rigorous pathological assessment. We detect a high frequency of mutation in CTNNB1 (43%), PIK3CA (43%), ARID1A (36%), PTEN (29%), KRAS (26%), TP53 (26%) and SOX8 (19%), a recurrently-mutated gene previously unreported in EnOC. POLE and mismatch repair protein-encoding genes were mutated at lower frequency (6%, 18%) with significant co-occurrence. A molecular taxonomy is constructed, identifying clinically distinct EnOC subtypes: cases with TP53 mutation demonstrate greater genomic complexity, are commonly FIGO stage III/IV at diagnosis (48%), are frequently incompletely debulked (44%) and demonstrate inferior survival; conversely, cases with CTNNB1 mutation, which is mutually exclusive with TP53 mutation, demonstrate low genomic complexity and excellent clinical outcome, and are predominantly stage I/II at diagnosis (89%) and completely resected (87%). Moreover, we identify the WNT, MAPK/RAS and PI3K pathways as good candidate targets for molecular therapeutics in EnOC.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome

et al. 2020

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“…10 A longitudinal analysis reported a median disease-specific survival of only 10.2 months for advanced-stage (International Federation of Gynecology and Oncology (FIGO) III/IV) clear cell carcinoma cases, compared with over 4 years for the overall clear cell carcinoma population. 26 The prognosis of patients with early-stage clear cell carcinoma is similar to or better than that of patients with serous carcinoma. 10 27-29 In a review of patients who participated in 12 prospective randomized Gynecologic Oncology Group (GOG) studies, progression-free survival was significantly better in clear cell carcinoma than in serous carcinoma, with a trend towards improved overall survival in stage I and II patients (progression-free survival hazard ratio (HR) 0.69, 95% CI 0.50 to 0.96; overall survival HR 0.76, 95% CI 0.53 to 1.09) 29 .…”

Section: Reviewmentioning

confidence: 99%

Clear cell carcinoma of the ovary: a clinical and molecular perspective

Iida

Okamoto

Hollis

et al. 2020

Int J Gynecol Cancer

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Clear cell carcinoma of the ovary has distinct biology and clinical behavior. There are significant geographical and racial differences in the incidence of clear cell carcinoma compared with other epithelial ovarian tumors. Patients with clear cell carcinoma are younger, tend to present at an early stage, and their tumors are commonly associated with endometriosis, which is widely accepted as a direct precursor of clear cell carcinoma and has been identified pathologically in approximately 50% of clear cell carcinoma cases. The most frequent and important specific gene alterations in clear cell carcinoma are mutations of AT-rich interaction domain 1A (ARID1A) (~50% of cases) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) (~50% cases). More broadly, subgroups of clear cell carcinoma have been identified based on C-APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) and C-AGE (age-related) mutational signatures. Gene expression profiling shows upregulation of hepatocyte nuclear factor 1-beta (HNF1β) and oxidative stress-related genes, and has identified epithelial-like and mesenchymal-like tumor subgroups. Although the benefit of platinum-based chemotherapy is not clearly defined it remains the mainstay of first-line therapy. Patients with early-stage disease have a favorable clinical outcome but the prognosis of patients with advanced-stage or recurrent disease is poor. Alternative treatment strategies are required to improve patient outcome and the development of targeted therapies based on molecular characteristics is a promising approach. Improved specificity of the histological definition of this tumor type is helping these efforts but, due to the rarity of clear cell carcinoma, international collaboration will be essential to design appropriately powered, large-scale clinical trials.

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“…Clinical data for the SHGSOC cohort was retrieved from the Edinburgh Ovarian Cancer Database 53 , the CRUK Clinical Trials Unit Glasgow and available electronic health records (ethics reference 15/ES/0094-SR751).…”

Section: Scottish High Grade Serous Ovarian Cancer (Shgsoc)mentioning

confidence: 99%

Structural Variants at theBRCA1/2Loci are a Common Source of Homologous Repair Deficiency in High-grade Serous Ovarian Carcinoma

Ewing

Meynert

Churchman

et al. 2021

Clinical Cancer Research

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Oncology and Cor2Ed; and is named on issued/pending patents relating to predicting treatment response in ovarian cancer unrelated to this work. R.G is or has been on the advisory boards of AstraZeneca, GSK, Tesaro and Clovis; has received speaker fees and funding to attend medical conferences from GSK and Tesaro and is a UK coordinating investigator or site principal investigator for studies sponsored by Astrazeneca, GSK, Pfizer and Clovis. F.N has been or is a site principal investigator for studies sponsored by AstraZeneca and Clovis. P.R has received research funding from AstraZeneca and Tesaro and honoraria/consultancy fees from AstraZeneca and GSK.

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Patterns of clinicopathological features and outcome in epithelial ovarian cancer patients: 35 years of prospectively collected data

Abstract: Objective Investigate the clinical landscape of ovarian carcinoma (OC) over time. Design Register-based prospectively collected data.

Cited by 32 publications

References 64 publications

Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome

Molecular stratification of endometrioid ovarian carcinoma predicts clinical outcome

Clear cell carcinoma of the ovary: a clinical and molecular perspective

Structural Variants at theBRCA1/2Loci are a Common Source of Homologous Repair Deficiency in High-grade Serous Ovarian Carcinoma

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