Gastric and Gastrointestinal-like Immunophenotypes In Conventional Endometrial Endometrioid Adenocarcinomas Including Endometrioid Adenocarcinomas with Mucinous Differentiation: Frequency and Diagnostic Implications

Abstract Introduction/Objective Mucinous carcinomas of the gastric/gastrointestinal type (MCG) are now recognized as a rare, clinically aggressive subtype of endometrial cancer [EMCa]. However, neither their full morphologic spectrum, nor their defining immunophenotype, has been clearly defined. Previous proposals for their recognition include at least focal immunohistochemical expression of gastrointestinal markers, minimality or absence of ER and possibly PAX8 expression, and the absence of an endometrioid carcinoma component. Herein, we assess the frequency of gastric and gastrointestinal immunophenotypes in conventional endometrioid carcinomas without any discernible gastric/gastrointestinal-type morphology. Methods/Case Report Immunohistochemical analyses for CK7, CK20, CDX2, ER, SATB2, MUC6, PAX8 were performed on 81 EMCa, comprised of consecutively archived cases of low grade endometrioid carcinoma (n=47), FIGO grade III endometrioid carcinoma (n=12), and endometrioid carcinomas with mucinous differentiation (n=22). None showed goblet cells or gastric-type morphology. Expression levels were quantified as H-scores on a standardized 0-300 scale. Results (if a Case Study enter NA) Significant subsets of all 3 groups showed expression of MUC6, CDX2, SATB2 and CK20, without any significant differences between the groups. 56%, 62%, 23% and 25% of cases expressed MUC6, CDX2, CK20 and SATB2 respectively. 37% co-expressed MUC6 and CDX2, 12% co-expressed CDX2 and CK20, 6% co-expressed MUC6, CDX2 and CK20 and 2.5% co-expressed CDX2, CK20 and SATB2. The expression levels were generally low across all groups, with average H scores for positive cases being 49.5 [range 1-250] for MUC6, 33.7 [range 1-285] for CDX2, 24.0 [range 1-270] for CK20, and 30.5 [range; 2-220] for SATB2. There was no statistically significant correlation between the expression of any of the 4 markers (CK20, CDX2, SATB2 or MUC6) and low ER or PAX8 expression. However, the only 2 cases with high CDX2 expression (H: >/=200) were also associated with low ER (H<50) expression, and one of these concurrently showed high CK20 (H: 270) and low PAX8 (H: 2) expression, suggestive of true intestinal differentiation. Conclusion MUC6, SATB2, CDX2, and CK20 are not uncommonly expressed at low levels in endometrioid carcinoma. As such, the expression of these markers cannot be the sole basis for defining the clinically aggressive EMCa with true gastric/gastrointestinal differentiation, and for distinguishing them from conventional endometrioid carcinomas.