Krämer, P;
Talhouk, A;
Brett, MA;
Chiu, DS;
Cairns, ES;
Scheunhage, DA;
Hammond, RF;
... Anglesio, MS; + view all
(2020)
Endometrial Cancer Molecular Risk Stratification is Equally Prognostic for Endometrioid Ovarian Carcinoma.
Clinical Cancer Research
, 26
(20)
pp. 5400-5410.
10.1158/1078-0432.CCR-20-1268.
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Abstract
Purpose: Endometrioid ovarian carcinoma (ENOC) is generally associated with a more favorable prognosis compared to other ovarian carcinomas. Nonetheless, current patient treatment continues to follow a "one-size-fits-all" approach. Even though tumor staging offers stratification, personalized treatments remain elusive. As ENOC shares many clinical and molecular features with its endometrial counterpart, we sought to investigate TCGA-inspired endometrial cancer (EC) molecular subtyping in a cohort of ENOC. Experimental Design: Immunohistochemistry and mutation biomarkers were used to segregate 511 ENOC tumors into four EC-inspired molecular subtypes: low-risk POLE mutant (POLEmut); moderate-risk mismatch repair deficient (MMRd); high-risk p53 abnormal (p53abn); moderate-risk with no specific molecular profile (NSMP). Survival analysis with established clinicopathological and subtypes specific features was performed. Results: 3.5% of cases were POLEmut, 13.7% MMRd, 9.6% p53abn and 73.2% NSMP, each showing distinct outcomes (p <0.001) and survival similar to observations in EC. Median OS was 18.1 years in NSMP, 12.3 years in MMRd; 4.7 years in p53abn and not reached for POLEmut cases. Subtypes were independent of stage, grade, and residual disease in multivariable analysis. Conclusions: EC-inspired molecular classification provides independent prognostic information in ENOC. Our findings support investigating molecular-subtype specific management recommendations for ENOC patients; for example, subtypes may provide guidance when fertility-sparing treatment is desired. Similarities between ENOC and EC suggest that ENOC patients may benefit from management strategies applied to EC and the opportunity to study those in umbrella trials.
| Type: | Article |
|---|---|
| Title: | Endometrial Cancer Molecular Risk Stratification is Equally Prognostic for Endometrioid Ovarian Carcinoma |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1158/1078-0432.CCR-20-1268 |
| Publisher version: | https://doi.org/10.1158/1078-0432.CCR-20-1268 |
| Language: | English |
| Additional information: | This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > Inst of Clinical Trials and Methodology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10106983 |
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