研究概要 |
We performed β-catenin immunostaining, methylation specific PCR for Wnt signaling associated genes such as AXIN2, APC, MCC and secreted frizzled-related proteins (SFRPs) in 27 Sessile serrated adenoma/polyps (SSA/Ps), 14 SSA/Ps with high grade dysplasia (SSA/P-HDs) and 9 SSA/Ps with submucosal carcinoma (SSA/P-CAs), as well as 19 conventional tubular adenomas (ADs), 26 ADs with high grade dysplasia (AD-HDs) and 25 ADs with submucosal carcinoma (AD-CAs). Nuclear β-catenin labeling was significantly lower in the SSA/P series than in their AD counterparts whereas a significant increment was found from SSA/Ps to SSA/P-HDs or SSA/P-CAs. The frequency of SFRP4 methylation was significantly higher in SSA/Ps, SSA/P-HDs and SSA/P-CAs, as compared to corresponding AD series. Although APC was only rarely methylated in all groups, AXIN2 and MCC were more frequently methylated in SSA/P-HDs and SSA/P-CAs than in AD counterparts. Stepwise increment of AXIN2 and MCC methylation was identified from SSA/Ps through SSA/P-HDs to SSA/P-CAs. A significant correlation was seen between nuclear β-catenin expression and methylation of AXIN2 or MCC in the SSA/P series. In conclusion, Wnt/β-catenin signal activation mediated by methylation of SFRP4, MCC and AXIN2 may make different contributions to colorectal neoplasia between the serrated and conventional routes.
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