Selective expression of gastric mucin MUC6 in colonic sessile serrated adenoma but not in hyperplastic polyp aids in morphological diagnosis of serrated polyps

Abstract

Colonic sessile serrated adenoma, in contrast to hyperplastic polyp, is thought to be related to sporadic colorectal cancers with high microsatellite instability. However, the morphological distinction between these entities is difficult and subject to observer and sampling variation. Therefore, we elected to investigate the expression of gastric mucin MUC6 as a potential marker to separate the two in the hope of finding an objective and reproducible adjunct to morphological diagnosis. Endoscopic biopsies of colonic polyps with serrated architecture, but without cytological dysplasia were studied and categorized as sessile serrated adenoma or hyperplastic polyp, using previously published morphological criteria. Smaller groups of serrated polyps with cytological dysplasia (traditional serrated adenomas, filiform serrated adenomas and sessile serrated adenomas with cytological dysplasia) were also included. In total, 94 polyps were immunohistochemically stained with antibodies to MUC6 and to MLH-1. MUC6 was found to have 100% specificity in distinguishing sessile serrated adenoma (N ¼ 26; positive staining) from hyperplastic polyp (N ¼ 48; negative staining). Traditional serrated adenomas and filiform serrated adenomas were also negative for MUC6. Sessile serrated adenomas with cytological dysplasia were found to lose expression of MLH-1 in dysplastic areas, while retaining MUC6 expression. Neither anatomic location in the right or left colon nor polyp size appears to account for the differences in MUC6 expression.

Risk factors in malignant transformation of gastric epithelial neoplasia categorized by the revised Vienna classification: endoscopic, pathological, and immunophenotypic features

“…In a recent report, phenotypic marker expression was closely associated with genetic alterations, especially microsatellite instability, which is signifi cantly associated with MUC6 expression. Moreover, MUC6 is upregulated by nuclear factor (NF)-κB, a nuclear transcription factor that is also activated in infl ammatory and neoplastic conditions [36][37][38]. It is noteworthy that positive immunoreactivity of MUC6 was found to be a risk factor for malignant change by the univariate and multivariate analyses in the present study.…”

Over-expression of cathepsin E and trefoil factor 1 in sessile serrated adenomas of the colorectum identified by gene expression analysis

“…In a recent study of SSAs, HPs and traditional SAs, expression of TFF1 was not discriminatory for SSAs and HPs nor was expression of MUC6 as demonstrated by immunohistochemistry [58]. However, other authors have claimed the MUC6 protein as being exclusively expressed in SSAs and not in HPs [59].…”

Serrated polyps of the colon and rectum (hyperplastic polyps, sessile serrated adenomas, traditional serrated adenomas, and mixed polyps)—proposal for diagnostic criteria

“…There is some controversy about the use of MUC6 staining, which was shown to distinguish HP (MUC6 negative) and SSA (MUC6 positive) in some studies [35]. More recent analyses revealed a relatively high specificity (82%), but relatively low sensitivity for MUC6-expression in SSAs [36].…”