Dataset Information

Clinicopathologic and Genomic Analysis of TP53-Mutated Endometrial Carcinomas.

ABSTRACT:

Purpose

Copy number-high endometrial carcinomas were described by The Cancer Genome Atlas as high-grade endometrioid and serous cancers showing frequent copy-number alterations (CNA), low mutational burden (i.e., non-hypermutant), near-universal TP53 mutation, and unfavorable clinical outcomes. We sought to investigate and compare the clinicopathologic and molecular characteristics of non-hypermutant TP53-altered endometrial carcinomas of four histologic types.

Experimental design

TP53-mutated endometrial carcinomas, defined as TP53-mutant tumors lacking microsatellite instability or pathogenic POLE mutations, were identified (n = 238) in a cohort of 1,239 endometrial carcinomas subjected to clinical massively parallel sequencing of 410-468 cancer-related genes. Somatic mutations and CNAs (n = 238), and clinicopathologic features were determined (n = 185, initial treatment planning at our institution).

Results

TP53-mutated endometrial carcinomas encompassed uterine serous (n = 102, 55.1%), high-grade endometrial carcinoma with ambiguous features/not otherwise specified (EC-NOS; n = 44, 23.8%), endometrioid carcinomas of all tumor grades (n = 28, 15.1%), and clear cell carcinomas (n = 11, 5.9%). PTEN mutations were significantly more frequent in endometrioid carcinomas, SPOP mutations in clear cell carcinomas, and CCNE1 amplification in serous carcinomas/EC-NOS; however, none of these genomic alterations were exclusive to any given histologic type. ERBB2 amplification was present at similar frequencies across TP53-mutated histologic types (7.7%-18.6%). Although overall survival was similar across histologic types, serous carcinomas presented more frequently at stage IV, had more persistent and/or recurrent disease, and reduced disease-free survival.

Conclusions

TP53-mutated endometrial carcinomas display clinical and molecular similarities across histologic subtypes. Our data provide evidence to suggest performance of ERBB2 assessment in all TP53-mutated endometrial carcinomas. Given the distinct clinical features of serous carcinomas, histologic classification continues to be relevant.

SUBMITTER: Momeni-Boroujeni A

PROVIDER: S-EPMC8530276 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Publications

Clinicopathologic and Genomic Analysis of <i>TP53</i>-Mutated Endometrial Carcinomas.

Momeni-Boroujeni Amir A Dahoud Wissam W Vanderbilt Chad M CM Chiang Sarah S Murali Rajmohan R Rios-Doria Eric V EV Alektiar Kaled M KM Aghajanian Carol C Abu-Rustum Nadeem R NR Ladanyi Marc M Ellenson Lora H LH Weigelt Britta B Soslow Robert A RA

Clinical cancer research : an official journal of the American Association for Cancer Research 20210218 9

<h4>Purpose</h4>Copy number-high endometrial carcinomas were described by The Cancer Genome Atlas as high-grade endometrioid and serous cancers showing frequent copy-number alterations (CNA), low mutational burden (i.e., non-hypermutant), near-universal <i>TP53</i> mutation, and unfavorable clinical outcomes. We sought to investigate and compare the clinicopathologic and molecular characteristics of non-hypermutant <i>TP53</i>-altered endometrial carcinomas of four histologic types.<h4>Experimen ...[more]

PMID: 33602681

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