Peroxisome proliferator-activated receptor γ is highly expressed in pancreatic cancer and is associated with shorter overall survival times

Abstract

Purpose: Peroxisome proliferator-activated receptor γ (PPAR-γ) is a ligand-activated transcription factor that has been implicated in carcinogenesis and progression of various solid tumors, including pancreatic carcinoma. We aimed to clarify the expression patterns of PPAR-γ in pancreatic ductal carcinomas and to correlate these to clinicopathologic variables, including patient survival. Experimental Design: Array-based expression profiling of 19 microdissected carcinomas and 14 normal ductal epithelia was conducted. Additionally, Western blots of pancreatic cancer cell lines and paraffinized tissue of 129 pancreatic carcinomas were immunostained for PPARγ. For statistical analysis, Fisher's exact test, χ2 test for trends, correlation analysis, Kaplan-Meier analysis, and Cox's regression were applied. Results: Expression profiles showed a strong overexpression of PPAR-γ mRNA (change fold, 6.9; P = 0.04). Immunohistochemically, PPARγ expression was seen in 71.3% of pancreatic cancer cases. PPARγ expression correlated positively to higher pT stages and higher tumor grade. Survival analysis showed a significant prognostic value for PPARγ, which was found to be independent in the clinically important subgroup of node-negative tumors. Conclusions: PPARγ is commonly up-regulated in pancreatic ductal adenocarcinoma and might be a prognostic marker in this disease. Both findings corroborate the importance of PPARγ in tumor progression of pancreatic cancer. © 2006 American Association for Cancer Research.