Wnt signaling pathway is activated in right colon serrated polyps correlating to specific molecular form of β-catenin

Abstract

The role of the Wnt signaling pathway in the tumorigenesis of sessile serrated adenoma (SSA) of the colorectum remains controversial. Using 2 antibodies targeting different epitopes (C-terminus and N-terminus), β-catenin expression in 35 SSAs and 30 right-sided hyperplastic polyps (RHPs) was examined by immunohistochemistry. Samples of 10 normal colorectal mucosa, 32 left-sided hyperplastic polyps, 27 traditional serrated adenomas (TSAs), and 40 traditional adenomas (TAs) were used as controls. Expression of adenomatous polyposis coli (APC) and mutated in colorectal cancer (MCC), key regulators of β-catenin, was also examined by immunohistochemistry. Using the C-terminus antibody, no nuclear staining of β-catenin was observed in any SSAs or RHPs. However, with the N-terminus antibody, accumulation of β-catenin was seen in 40.0% of SSAs and 33.3% of RHPs. The average immunoreactivity score of APC in SSAs (67.0 ± 21.6) and RHPs (69.2 ± 24.4) was significantly higher than that in TAs (22.0 ± 18.0) and TSAs (49.5 ± 23.1; all P < .05). In contrast, MCC was more frequently lost in right-sided-polyps such as SSA and RHP than in left-sided polyps such as left-sided hyperplastic polyp, TSA, and TA. Our results suggest that Wnt signaling is activated in SSA and its possible precursor lesion RHP. The present study also implied that the specific molecular form of β-catenin may participate in the Wnt signaling activation of right-sided serrated polyps. Moreover, loss of MCC expression but not APC may contribute to the early activation of Wnt signaling in right-sided serrated polyps.