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Molecular subtypes of clear cell carcinoma of the endometrium: Opportunities for prognostic and predictive stratification.

Abstract：

OBJECTIVE:Our aim was to characterize the pathological, molecular and clinical outcomes of clear cell carcinoma of the endometrium (CCC). METHODS:CCC underwent ProMisE (Proactive Molecular Risk Classifier for Endometrial Cancer) classification identifying four molecular subtypes: i) 'POLEmut' for ECs with pathogenic POLE mutations, ii) 'MMRd', if there is loss of mismatch repair proteins by immunohistochemistry (IHC), iii) 'p53wt' or iv) 'p53abn' based on p53 IHC staining. Clinicopathologic parameters, immune markers (CD3, CD8, CD79a, CD138, PD-1), ER, L1CAM, and outcomes were assessed. RESULTS:52 CCCs were classified, including 1 (2%) POLEmut, 5 (10%) MMRd, 28 (54%) p53wt and 18 (35%) p53abn. Women with p53abn and p53wt CCCs were older than women with MMRd and POLEmut subtypes. p53wt CCC were distinct from typical p53wt endometrioid carcinomas; more likely to arise in older, thinner women, with advanced stage disease, LVSI and lymph node involvement, and a higher proportion ER negative, L1CAM overexpressing tumors with markedly worse outcomes. High levels of immune infiltrates (TILhigh) were observed in 75% of the CCC cohort. L1CAM overexpression was highest within p53abn and p53wt subtypes of CCC. CONCLUSION:CCC is a heterogeneous disease encompassing all four molecular subtypes and a wide range of clinical outcomes. Outcomes of patients with POLEmut, MMRd and p53abn CCC are not distinguishable from those of other patients with these respective subtypes of EC; p53wt CCC, however, differ from endometrioid p53wt EC in clinical, pathological, molecular features and outcomes. Thus, p53wt CCC of endometrium appear to be a distinct clinicopathological entity within the larger group of p53wt ECs.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Kim SR,Cloutier BT,Leung S,Cochrane D,Britton H,Pina A,Storness-Bliss C,Farnell D,Huang L,Shum K,Lum A,Senz J,Lee CH,Gilks CB,Hoang L,McAlpine JN

doi

10.1016/j.ygyno.2020.04.043

subject

Has Abstract

pub_date

2020-07-01 00:00:00

pages

3-11

issue

eissn

0090-8258

issn

1095-6859

pii

S0090-8258(20)30302-4

journal_volume

158

pub_type

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Molecular subtypes of clear cell carcinoma of the endometrium: Opportunities for prognostic and predictive stratification.