The Clinical Significance of Transforming Growth Factor (TGF) beta1, TGF beta Receptor beta II, p53 Protein and K-ras Point Mutation in Pancreatic Cancer

ABSTRACT

PURPOSE: Many cancers, including pancreatic cancer, harbor defects in TGF beta signaling and are resistant to TGF beta mediated growth inhibition. In addition, the expression of the p53 gene and mutations in K-ras might play an important role in the multistep carcinogenesis of pancreatic cancer. This study examined the expression level of TGF beta 1, TGF beta receptorII (T beta RII), p53 protein and K-ras mutation in pancreatic cancer, along with their role and clinical significance. METHODS: The overexpression of TGF beta 1, T beta RII and p53 protein was evaluated using an immunohistochemical assay. The K-ras mutation was analyzed by PCR-RFLP in the surgical resected pancreatic tissue from 26 pancreatic ductal adenocarcinomas and 5 normal pancreases. RESULTS: Immunohistochemical analysis of TGF beta 1 and T beta RII revealed positive immunostaining in 73.1% and 76.9% of the tumors, respectively, which were significantly higher than the normal pancreas (P=0.008). The p53 protein was positive in none of the 5 normal ducts and 16 out of 26 (61.5%) pancreatic carcinoma specimens. The K-ras mutation was positive in none of the 5 normal ducts, and in 20 of the 26 pancreatic carcinoma specimens (76.9%). The presence of TGF beta1 and T beta RII in the cancer samples was significantly associated with node metastasis, advanced tumor stage (P<0.01), and a short survival time (P<0.05). The p53-positive pancreatic cancers showed a significantly lower survival rate than those with p53-negative tumors (P<0.05). There was no correlation between K-ras mutations and the survival rates. CONCLUSION: The detection of K-ras mutations and TGF beta 1, T beta RII and p53 protein overexpression can predict the prognosis of pancreatic carcinoma patients.