The Clinical Significance of Transforming Growth Factor (TGF) β1, TGFβ ReceptorβII, p53 Protein and K-ras Point Mutation in Pancreatic Cancer

Abstract

Purpose: Many cancers, including pancreatic cancer, harbor defects in TGF? signaling and are resistant to TGF? 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?1, TGF? receptorII (T?RII), p53 protein and K-ras mutation in pancreatic cancer, along with their role and clinical significance. Methods: The overexpression of TGF?1, T?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?1 and T?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?1 and T?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?1, T?RII and p53 protein overexpression can predict the prognosis of pancreatic carcinoma patients.