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Peroxisome Proliferator-Activated Receptor Is Highly Expressed in Pancreatic Cancer and Is Associated With Shorter Overall Survival Times

Authors' Affiliations: ¹ Institute of Pathology and ² Department of Surgery, Charité University Hospital, Berlin, Germany; ³ Department of Visceral, Thoracic, and Vascular Surgery, University Hospital Dresden, Dresden, Germany; and ⁴ Institute of Pathology, University of Schleswig-Holstein Campus Kiel, Kiel, Germany

Requests for reprints: Glen Kristiansen, Institute of Pathology, Charité University Hospital, Schumannstrasse 20/21, 10117 Berlin, Germany. Phone: 49-30-450-53-6145; Fax: 49-30-450-53-6945; E-mail: glen.kristiansen{at}charite.de.

Purpose: Peroxisome proliferator-activated receptor (PPAR) 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 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 PPAR. For statistical analysis, Fisher's exact test, ² test for trends, correlation analysis, Kaplan-Meier analysis, and Cox's regression were applied.

Results: Expression profiles showed a strong overexpression of PPAR mRNA (change fold, 6.9; P = 0.04). Immunohistochemically, PPAR expression was seen in 71.3% of pancreatic cancer cases. PPAR expression correlated positively to higher pT stages and higher tumor grade. Survival analysis showed a significant prognostic value for PPAR, which was found to be independent in the clinically important subgroup of node-negative tumors.

Conclusions: PPAR is commonly up-regulated in pancreatic ductal adenocarcinoma and might be a prognostic marker in this disease. Both findings corroborate the importance of PPAR in tumor progression of pancreatic cancer.