Mutational spectrum of K-ras oncogene among Indian patients with gallbladder cancer

Background and Aim: Gallbladder cancer (GBC) is a common abdominal malignancy in India with an obscure etiology. However, long-standing stones and chronic infection in gallbladder have been suspected as possible etiologic factors. As carcinogenesis complicating chronic inflammation proceeds through the stages of dysplasia and metaplasia, mutation in the K-ras gene may be an important marker for GBC. The aim of the present study was to detect K-ras mutation in cytological smears from GBC. Methods: Malignant cells were marked on slides of cytological smears obtained from 39 patients with cytologically proven GBC. Marked cells were scraped off and DNA was extracted. Polymerase chain reaction coupled with restriction fragment length polymorphism (RFLP) analysis was performed to detect the point mutation in codon 12 of the K-ras gene. Results: Mutation in codon 12 of K-ras oncogene was detected in eight (38%) of 21 PCR amplified samples by this technique. Six of eight specimens with K-ras (codon 12) mutation corresponded to coexisting gallstone disease. Five patients with K-ras (codon 12) mutation were found to have stage IV malignancy. Conclusions: Mutation in codon 12 of the K-ras oncogene occurs in more than one-third of GBC in northern India. Its detection from fine-needle aspirates may prove useful as an adjunct to cytological examination. The presence of this mutation suggests that chronic inflammation may play an etiologic role in gallbladder carcinogenesis. (C) 2004 Blackwell Publishing Asia Pty Ltd.