Significance of K-ras Mutation and p53 Protein Expression in Pancreatic Adenocarcinoma

Kim, Young Chul; Choi, Kwang Ho

Abstract

BACKGROUND: Activation of the K-ras oncogene by specific point mutations at codon 12 occurs at a remarkably high frequency in pancreatic adenocarcinomas. Also, inactivation of the p53 suppressor gene function in pancreatic adenocarcinomas leads to the loss of cellular proliferation regulation and to the induction of cell death. Though K-ras mutation and inactivation of the p53 suppresser gene have been considered to be events in the oncogenesis of a pancreatic adenocarcinoma, whether their association with differences or survival in pancreatic adenocarcinoma is controversial. We investigated the presence of K-ras mutation and overexpression of p53 protein in the carcinogenesis of a pancreatic adenocarcinoma. Also, their correlations with tumor grade, stage, and survival were investigated.
METHODS
We examined surgically resected, formalin-fixed, paraffin-embedded pancreatic adenocarci nomas from 48 patients. By using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), we detected a K-ras oncogene mutation at codon 12. An overexpression of p53 protein was detected by using an immunohistochemical staining (IHC) method with anti-p53 monoclonal antibody.
RESULTS
K-ras oncogene mutation at codon 12 was detected in 64.6% of the cases and p53 protein was overexpressed in 47.9%. Both K-ras oncogene mutation and p53 protein overexpression were detected in 29.2% of the cases. There was no correlation between the rate of K-ras mutation and tumor grade, T category (tumor size or depth of invasion), N category (lymph-node metastasis) and clinical stage. Also, K-ras mutation was not correlated with the survival rate. A positive correlation between p53 protein overexpression and clinical stage was found (p<0.05). The patients with p53 protein overexpression had a shorter survival than the patients without p53 protein overexpression (p>0.05).
CONCLUSION
The mutation of the K-ras oncogene and p53 suppresser gene might play an important role in pancreatic carcinogenesis. However, the mutation of the K-ras oncogene is not thought to be related to the progression of a pancreatic adenocarcinoma and the corresponding survival rate. It is suggested that overexpression of the p53 protein seems to be associated with the progression of pancreatic adenocarcinoma.