Genetic Changes of P53 and Kras in Gallbladder Carcinoma in Kumaon Region of Uttarakhand

Abstract

Background: Gallbladder carcinoma is a highly lethal but relatively rare neoplasm of the digestive tract. p⁵³ mutations are one of the most frequent genetic alterations in human cancers and are thought to play a role in pathogenesis of several malignancies. Kras oncogene is responsible for high frequency recognized as an early event in pancreatic and colonic carcinogenesis.

Objectives: We investigated the genetic change of p⁵³, Kras and histopathological changes in gallbladder cancer tissue samples.

Methods: P⁵³ mutation was seen in the axons 5, 6, 7 and 8 of p⁵³ gene and Kras codon 12 mutations in 25 operative specimens of gallbladder carcinoma. The hispathology observations and polymerase chain reaction-based techniques of these patients were used for point mutations study in p⁵³ and in codon 12 of Kras gene.

Results: Mutations of p⁵³ analyzed from exons 5 to 8 using the method of PCR-SSCP were 44%, PCR-RFLP was carried out, and incidence of mutation in codon 12 of Kras was 48% in the adenocarcinoma patients. There was a significant correlation between presence of gall stone, histopathological type, cellular differentiation, grade, lymphovascular invasion, perineural invasion, lymph node invasion, involvement of cystic duct end margin, liver invasion, omental tissue invasion, and T.N.M. staging.

Conclusions: Curative surgical resection remains the only effective approach for treatment of GBC. Studies with large number of cases with latest application, next-generation sequencing, DNA microarray, transcriptome analysis, and real-time PCR would help in exploring more targets and better classification of these cancers at genetic level.

Keywords: Carcinoma; Cholecystectomy; Gallbladder; Treatment.