Gene mutations of K-ras in gallbladder mucosae and gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct

OBJECTIVE: In this study, we examined the mutational spectrum of K-ms in ca ses of gallbladder and gallbladder carcinoma with an anomalous junction of the pancreaticobiliary duct (AJPBD). METHODS: We examined 35 gallbladders with AJPBD (20 with hyperplasia, 15 wi th carcinoma) and 38 gallbladders without AJPBD (four normal gallbladders, four with hyperplasia, six with adenoma, 24 with carcinoma). Polymerase cha in reaction single-strand conformation polymorphism (PCR-SSCP) and direct s equencing were performed to detect mutations in codon 12 or 13 of K-ras. RESULTS: In the cases with AJPBD, the prevalences of K-ras mutation were 15 % (3/20) in hyperplasia, 60% (6/10) in stage I carcinoma, and 100% (5/5) in stage II-IV carcinoma. In the cases without AJPBD, the prevalences of K-ra s mutation were 0% (0/4) in normal gallbladder, 0% (0/4) in hyperplasia, 17 % (1/6) in adenoma, 7% (1/16) in stage I carcinoma, and 38% (3/8) in stage II-IV carcinoma. Prevalences of K-ras mutation in hyperplasia and carcinoma with AJPBD were greater than those without AJPBD (p < 0.05). The point mut ation of GGT to GAT in codon 12 was frequently observed in the cases with A JPBD. CONCLUSION: These results suggest that the specific K-ras mutation in codon 12 (GGT to GAT) may contribute to the early stage of carcinogenesis in the gallbladder with AJPBD. (Am J Gastroenterol 1999,94.1638-1642. (C) 1999 by Am. Cell. of Gastroenterology).