Characterization of Gastric/Gastrointestinal-Like Immunophenotypes in Endometrial Endometrioid Adenocarcinomas, Including Endometrioid Adenocarcinomas with Mucinous Differentiation.

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Endometrial mucinous carcinoma of the gastric [gastrointestinal] type (MCG) is a rare, possibly aggressive subtype of endometrial cancer that should be distinguished from its potential mimics, including endometrioid carcinoma (EEC). Herein, we assess the frequency of gastric and gastrointestinal immunophenotypes in EEC without any discernible gastric/gastrointestinal-type morphology. Immunohistochemical analyses for KRT(CK)7, KRT20, CDX2, ER, SATB2, MUC6, PAX8, and HIK1083 were performed on 81 EEC, inclusive of consecutively archived low grade [with (n=22) and without (n=47) mucinous differentiation] and high grade (n=12) cases. None displayed gastric-type morphology or goblet cells. Expression levels were semi-quantified as H-scores (combining intensity and extent of staining) on a standardized 0-300 scale. Among the gastric/gastrointestinal-type markers, 56%, 62%, 23%, 25%, and 0% of cases expressed MUC6, CDX2, KRT20, SATB2, and HIK1083 respectively. The expression levels for positive cases were generally low, with average H-scores being 49.5 [range 1-250] for MUC6, 33.7 [1-285] for CDX2, 24.0 [1-270] for CK20, and 30.5 [2-220] for SATB2. Ten (12.35%) cases showed high expression (H ≥200) of at least 1 gastric/gastrointestinal-type marker, including 1, 2, 2 and 6 cases that were high positive for KRT20, SATB2, CDX2 and MUC6 respectively. Immunoreactive foci were generally indistinguishable from background at the morphologic level. There was no statistically significant correlation between the expression of any of the gastric/gastrointestinal-type markers and ER, KRT7 or PAX8 expression. In summary, gastric/gastrointestinal-type proteins are not uncommonly expressed at low levels in EEC. As such, positivity for these markers cannot be the sole basis for distinguishing EEC from MCG.