“Clear Cell Change” in Colonic Tubular Adenoma and Corresponding Colonic Clear Cell Adenocarcinoma Is Associated with Decreased MUC2 and MUC5 Expression
C Shi, JR Scudiere, T Cornish, D Lam-Himlin, JY Park, E Montgomery. Johns Hopkins Hospital, Baltimore, MD; Caris Diagnostics, Boston
Background: Focal clear cell change is seen in a small subset of colonic tubular adenomas (TAs). Adenocarcinomas arising from these lesions can also demonstrate a clear cell phenotype. This clear cell change has not been well characterized.
Design: We characterized clear cell changes found in colonic TAs and associated invasive clear cell adenocarcinomas by immunohistochemical labeling. Ten TAs, all with at least focal clear cell change with/without associated invasive adenocarcinoma, from 9 patients formed the basis of this study. Formalin-fixed, paraffin-embedded tumor sections were stained with PAS/PAS-diastase and immunolabeled with antibodies to MUC2, MUC5, MUC6, CK7, CK20 and CDX2.
Results: Seven of 10 (70%) TAs with focal clear cell change had focal to extensive high-grade dysplasia. Two of the adenomas had an associated invasive clear cell adenocarcinoma. The adenomas/carcinomas ranged from 0.5 to 3.5 cm. PAS/PAS-diastase stains showed minimal PAS(+) materials in the clear cells. Immunohistochemical studies demonstrated that the clear cells had decreased MUC2 labeling compared to the surrounding conventional adenoma in 8 cases (8/10, 80%), including the two clear cell adenocarcinomas, and decreased MUC5 labeling in 3 of 3 cases (100%) with positive MUC5 labeling in the background TA. No immunoreactivity to MUC6 was observed in either the clear cells or background TAs. Compared to background TAs, both increased and decreased expression of CK7 and CK20 were observed in areas with clear cell change. Decreased CDX2 expression in the clear cells was seen in 4 of 9 (44%) TAs with positive CDX2 labeling of the background adenoma. One of the clear cell carcinomas was CK20+, CK7-, CDX2+ and the other was CK20+. CK7-, CDX2 - focal positive.
Conclusions: The clear cells seen in some colonic TAs have different immunophenotypic characteristics than the associated background adenomatous epithelium. Invasive clear cell adenocarcinomas arising from these lesions share morphologic and immunohistochemical features with the clear cell change in the TAs although both clear cell adenocarcinomas retained the typical CK20(+)/CK7(-) profile of conventional adenocarcinomas. Our results indicate that clear cell adenocarcinomas can be primary in the colorectum with identifiable precursors. Awareness of them and their immunoprofile allows distinction from clear cell lesions from other sites.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 70, Wednesday Morning