1. Clinicopathologic and Genomic Analysis of TP53-Mutated Endometrial Carcinomas
- Author
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Lora H. Ellenson, Carol Aghajanian, Robert A. Soslow, Marc Ladanyi, Eric Rios-Doria, Nadeem R. Abu-Rustum, Kaled M. Alektiar, Chad M. Vanderbilt, Sarah Chiang, Britta Weigelt, Rajmohan Murali, Amir Momeni-Boroujeni, and Wissam Dahoud
- Subjects
0301 basic medicine ,Cancer Research ,Pathology ,medicine.medical_specialty ,Massive parallel sequencing ,endocrine system diseases ,biology ,business.industry ,Not Otherwise Specified ,Microsatellite instability ,SPOP ,medicine.disease ,03 medical and health sciences ,Serous fluid ,030104 developmental biology ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Carcinoma ,medicine ,biology.protein ,PTEN ,business ,Clear cell - 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.
- Published
- 2021
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