Differences in mucus and K-ras mutation in relation to phenotypes of tumors of the papilla of Vater

Abstract

To investigate their hypothesis that K-ras mutation is correlated with epithelial metaplastic change, the authors classified tumors of the papilla of Vater histologically and according to mucin histochemistry as either intestinal type (complete or incomplete) or pancreaticobiliary type (ordinary or metaplastic) and analyzed the tumors for K-ras mutation during tumorigenesis. Fifty-two tumors of the papilla of Vater (5 adenomas, 24 carcinomas with adenoma component, and 23 carcinomas) obtained from surgical specimens were evaluated. The mucus phenotype was analyzed with MUC1, MUC2, MUC5AC, sialyl Lewis(a) (CA 19-9), HID-AB, and ConA III stainings. K-ras codon 12 mutation was detected by nested polymerase chain reaction (PCR)-restriction fragment length polymorphism and enriched PCR-enzyme-linked minisequence assay. The presence of adenoma component and intramucosal tumor spreading in the ampulloduodenum was significantly higher in intestinal-type tumors (90%, 27 of 30 tumors, and 100%, 30 of 30 tumors, respectively) than in pancreaticobiliary-type tumors (9%, 2 of 22 tumors, and 23%, 5 of 22 tumors, respectively) (P < 0.0001). MUC2 expression was positive in intestinal-type tumors but not in pancreaticobiliary-type tumors. K-ras mutation rates for incomplete intestinal-type tumors (78%, 7 of 9) and metaplastic pancreaticobiliary-type tumors (64%, 7 of 11), which showed MUC5AC (gastric-type apomucin) expression in cytoplasm, were significantly higher than in complete intestinal-type tumors (33%, 6 of 21) and ordinary pancreaticobiliary-type tumors (18%, 2 of 11) (P = 0.01 and P = 0.03, respectively). In pancreaticobiliary-type tumors, K-ras mutation was more frequently recognized in tumors with ampullopancreatic duct tumor extension (75%, 3 of 4) than in those with ampullobiliary duct extension (0%, 0 of 6) (P = 0.01). Furthermore, sequences of K-ras codon 12 were common in 17 carcinomas with adenoma component that were analyzed for both adenoma and carcinoma. Tumors of the papilla of Vater can be classified histologically as either intestinal type or pancreaticobiliary type, and they have different features according to tumor location, association with adenoma, and MUC2 expression. Furthermore, K-ras mutation is supposed to be associated with tumors arising in the area from the ampulloduodenum to the ampullopancreatic duct, with metaplastic mucus occurring in both intestinal and pancreaticobiliary types.