Synapse - Clinicopathologic and genomic analysis of TP53-mutated endometrial carcinomas

Clinicopathologic and genomic analysis of TP53-mutated endometrial carcinomas Journal Article

Authors:	Momeni-Boroujeni, A.; Dahoud, W.; Vanderbilt, C. M.; Chiang, S.; Murali, R.; Rios-Doria, E. V.; Alektiar, K. M.; Aghajanian, C.; Abu-Rustum, N. R.; Ladanyi, M.; Ellenson, L. H.; Weigelt, B.; Soslow, R. A.
Article Title:	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), nearuniversal 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. © 2021 American Association for Cancer Research.
Journal Title:	Clinical Cancer Research
Volume:	27
Issue:	9
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2021-05-01
Start Page:	2613
End Page:	2623
Language:	English
DOI:	10.1158/1078-0432.Ccr-20-4436
PUBMED:	33602681
PROVIDER:	scopus
PMCID:	PMC8530276
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85105268071&doi=10.1158%2f1078-0432.CCR-20-4436&partnerID=40&md5=483e104077f4fbff67b35a1daa938161
Notes:	Article -- Export Date: 1 June 2021 -- Source: Scopus