This result may suggest that the activation of the PIK3CA-protein kinase B signaling pathway, in addition to the abrogation of p53, SMAD4 and RAS mitogen-activated protein kinase may have a crucial role in the carcinogenesis of Japanese BTC.
Immunohistochemical studies for Madh4 protein in nine archival cancers (six pancreatic cancers, two duodenal cancers, and one biliary cancer) with known missense mutations indicated that all mutations within the MH1 or MH2 domain COOH-terminal to the MCR (seven of nine cases) had negative or weak labeling, whereas two cancers with mutations within the MCR had strong positive nuclear labeling for Madh4 protein.