Molecular findings in endometrial mucinous carcinoma of the gastric [Gastrointestinal] type: A report of 5 additional cases and a systematic review of the literature

Abstract

The authors summarize the somatic mutational landscape of endometrial mucinous carcinoma of the gastric (gastrointestinal) type [MCG], based on findings from a 5-case cohort and a systematic review of the literature, the latter including 25 cases from 3 published reports. The 30 cases were analyzed by variably-sized next generation sequencing gene panels, and featured 74 total mutations, including 20 unique mutations [mean 2.47 ± 1.14 mutations/case; median= 2; range 1–5]. Mutations that were identified in > 1 case included TP53 (20/30, 66.7 %), KRAS (11/30, 36.7 %), PIK3CA (9/30, 30 %), BRCA2 (4/30, 13.3 %), STK11 (4/30, 13.3 %), ERBB2 (3/30, 10 %), SMAD4 (3/30, 10 %), FBXW7 (3/30, 10 %), ATM (3/30, 10 %), PTEN (2/30, 6.7 %), ARID1A (2/30, 6.7 %), and CDKN2A (2/30, 6.7 %). The most commonly reported combination of mutations [irrespective of the concurrent presence of other mutations] included KRAS + TP53 (9/30, 30.0 %), PIK3CA + TP53 (4/30, 13.3 %), SMAD4 + TP53 (3/30, 10 %), STK11 + TP53 (3/30, 10 %). Regarding molecular classification, most cases (20/30, 66.7 %) were p53-abnormal, with smaller subsets being dMMR (10 %), of “no specific molecular profile” (6/30, 20 %), and POLE mutated (1/30, 3.3 %). In summary, MCG may display a spectrum of mutations of potential clinicopathologic significance. TP53, KRAS and PIK3CA are the most commonly mutated genes in MCG. The four molecular subclasses of endometrial carcinoma are represented in MCG, with p53-abnormal being predominant. Our findings highlight the molecular landscape of this rare and incompletely characterized entity.