Prognostic Significance of K-<b><i>ras</i></b> Codon 12 Mutation in Patients with Resected Gallbladder Cancer

Abstract

Background: Point mutation of K-ras is associated with carcinogenesis and overall survival in various cancers. We investigated the mutational spectrum of K-ras codon 12 in resected normal and gallbladder cancer tissue samples in a Northern Indian population and correlated it with different clinicopathological parameters. Patients and Methods: Gallbladder tissues from normal (n = 24) and cancer patients (n = 39) were analyzed for K-ras codon 12 mutation by restriction fragment length polymorphism. Statistical analysis was carried out using the χ² test or Fisher's exact test. Survival was estimated using the Kaplan-Meier method, and the difference between survival curves was analyzed by the log-rank test. Results: The frequency of K-ras mutation was significantly higher (p = 0.001) in gallbladder cancer tissue samples (16/39) compared to normal samples (1/24). Patients with K-ras mutation had a significantly decreased overall survival (p = 0.003), particularly for stage II (p = 0.021) and III (p = 0.009) cancers. No significant correlation was observed with any of the other clinicopathological factors studied. Conclusions: Gallbladder cancer has a high frequency of K-ras codon 12 mutation with poorer outcomes in resected stage II and III disease. K-ras mutational analysis has important prognostic implications that need to be investigated further.

Differential Expression of Cholecystokinin A Receptor in Gallbladder Cancer in the Young and Elderly Suggests Two Subsets of the Same Disease?

“…Decrease in CCK receptors may be involved in the pathogenesis of gallstone formation resulting in decreased gallbladder motility. It has been observed that gallstones are present in nearly 80% of patients with GBC [11, 12]. Moreover, abnormal processing of CCKAR is found to be associated with gallstones and obesity [13].…”

Tumor Protein p53 and K-ras Gene Mutations in Peruvian Patients with Gallbladder Cancer

“…This mutation plays an important role in the early stage of carcinogenesis of biliary mucosa, especially in association with AUPBD (Sagawa et al, 1998). Therefore, the frequency of K-ras mutation has widely been reported to be 0% to 41% in gallbladder cancer patients according to the presence or absence of the AUPBD (Kim et al, 2001;Deshpande et al, 2011;Kazmi et al, 2013). A significant difference in the frequency of this mutation has been reported between gallbladder cancer patients with and without AUPBD in a previous study (Hanada et al, 1999).…”

“…It is converted to an active oncogene through point mutations concentrated in codons 12, 13, and 61 by some carcinogens (Stolze et al, 2015). The frequency of K-ras mutations in gallbladder cancer patients was reported to be 0% to 41% (Kim et al, 2001;Deshpande et al, 2011;Kazmi et al, 2013). However, to our knowledge, data on the associations between these mutations and gallbladder cancer in Peru are limited.…”

Elevated Expression of Maspin mRNA as a Predictor of Survival in Stage II and III Gallbladder Cancer Cases

“…Gallbladder cancer (GBC) is the most common malignancy of biliary tract with marked ethnic and geographical variations including Northern Indian gangetic belt (Pandey et al, 2001;Misra et al, 2003;Gupta et al, 2012;Kazmi et al, 2013). Poor prognosis due to late diagnosis and early dissemination is the common characteristic of this dreaded disease (Dhir and Mohandas, 1999).…”