RAS GENE POINT MUTATIONS IN GALLBLADDER LESIONS ASSOCIATED WITH ANOMALOUS CONNECTION OF PANCREATICOBILIARY DUCTS

Background/Aims: The present study was undertaken to investigate possi ble changes in, the K-ras oncogene in patients with gallbladder lesion s (carcinoma, adenoma or hyperplasia) in. relation to the presence or absence of an anomalous connection of pancreatobiliary ducts (ACPBD). Methodology: Gallbladder specimens were obtained from 44 patients with lesions that were either with or without ACPBD, and DNA samples were analyzed using PCR-SSCP. Point mutations in, codons 12, 13 and 61 were analyzed by direct sequencing methods with oligonucleotide primers. R esults: The K-ras codon 12 was detected in 83.3% (5/6) of carcinomas, the one adenoma tested and in 35.7% (5/14) of hyperplastic lesions wit h ACPBD, as opposed to only 36.4% (4/11) of carcinomas without ACPBD. The one case of gallbladder adenoma and 11 cases of normal gallbladder without ACPBD studied demonstrated no point mutations in the K-ras on cogene. Conclusions: Alteration of the K-ras oncogene appears to be in volved in the early stages of gallbladder carcinogenesis when in, asso ciation. with ACPBD. The results further suggest that hyperplasia in. cases with ACPBD may be a significant pre-cancerous lesion.