Peroxisome proliferator-activated receptor gamma is highly expressed in pancreatic cancer and is associated with shorter overall survival times.
OBJECTIVE
Peroxisome proliferator-activated receptor gamma (PPARgamma) 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 PPARgamma in pancreatic ductal carcinomas and to correlate these to clinicopathologic variables, including patient survival.


METHODS
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 PPARgamma. For statistical analysis, Fisher's exact test, chi2 test for trends, correlation analysis, Kaplan-Meier analysis, and Cox's regression were applied.


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


CONCLUSIONS
PPARgamma is commonly up-regulated in pancreatic ductal adenocarcinoma and might be a prognostic marker in this disease. Both findings corroborate the importance of PPARgamma in tumor progression of pancreatic cancer.
Kristiansen
Glen
G
Institute of Pathology and Department of Surgery, Charité University Hospital, Berlin, Germany. glen.kristiansen@charite.de
Jacob
Juliane
J
Buckendahl
Ann-Christin
AC
Grützmann
Robert
R
Alldinger
Ingo
I
Sipos
Bence
B
Klöppel
Günter
G
Bahra
Marcus
M
Langrehr
Jan M
JM
Neuhaus
Peter
P
Dietel
Manfred
M
Pilarsky
Christian
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D047495:PPAR gamma; D012333:RNA, Messenger