Re-classification of pancreatobiliary tumors by mucin expression profile - An application to the operative indication -

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We examined the expression profiles of membrane mucins (MUC1 and MUC4) and secretory mucins (MUC2, MUC5AC and MUC6) hi many pancreatobiliary tumors, and compared the results with clinicopathological factors of the patients with those tumors.In pancreatic tumors, we examined mucins expression in invasive ductal carcinomas (IDCs) and intraductal papillary mucinous neoplasms (IPMNs) using immunohistochemistry and in situ hybridization. IPMNs were classified into two histological subtypes, "dark cell type (IPM N-D" and "clear cell type (IPMN-C). IDCs showed high expression of all the glycoforms of MUC1. IPMNs-D showed no or low expression of all the glycoforms of MUC1. IPMNs-C showed low expression of poorly glycosylated MUC1 (MUC1/DF3), but expression of glycosylated MUC1 (MUC1/HMFG-1). Expression of MUC2 was negative in IDC, high in IPMN-D and low in IPMN-C. MUC5AC was highly expressed in all the types. MUC6 expression was higher in IPMNs-C than in IDCs and IPMNs-D.In intrahepatic cholan … More giocarcinoma-mass forming type, MUC4 expression was a statistically significant independent risk factor. Mucin-producing bile duct tumors were classified into two distinct categories by the histopathological findings, morphometry and mucin expression profiles, and there was a significant difference of the survivals between the two patient groups with two different tumors. In the patients with extrahepatic bile duct carcinomas, MUC1/DF3 was the most useful prognosis indicator among the various glycoforms of MUC1 mucins. For the comparative studies with the pancreatobiliary tumors, we also studied expression profiles of mucins in the tumors of other organs such as colon, breast, etc.To investigate the expression mechanism of MUC2 in the tumors, we examined DNA methylation in promotor areas of MUC2 gene in pancreatic carcinoma cells with MUC2 + or - expression, using methylation specific PCR. The promotor area of MUC2 gene was unmethylated in pancreatic carcinoma calls with MUC2 + expression, whereas it was methylated in pancreatic carcinoma cells with MUC2 - expression. Expression mechanism of MUC2 in the pancreatic tumors may be regulated by DNA methylation in the promptor areas of MUC2 gene. We also could amplify DNA from a small amount of tissues obtained by microdissection. Less