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  • Title: Peroxisome proliferator-activated receptor-gamma and retinoid X receptor-alpha expression in pancreatic ductal adenocarcinoma: association with clinicopathological parameters, tumor proliferative capacity, and patients' survival.
    Author: Giaginis C, Katsamangou E, Tsourouflis G, Zizi-Serbetzoglou D, Kouraklis G, Theocharis S.
    Journal: Med Sci Monit; 2009 May; 15(5):BR148-56. PubMed ID: 19396032.
    Abstract:
    BACKGROUND: Peroxisome proliferator-activated receptor-gamma (PPAR-gamma), a ligand-activated transcription factor that forms heterodimers with the retinoid X receptors (RXRs), is overexpressed in various tumors, regulating many aspects of cancer biology. The aim of the present study was to evaluate the clinical significance of PPAR-gamma and RXR-alpha expression in pancreatic adenocarcinoma. MATERIAL/METHODS: PPAR-gamma and RXR-alpha protein expression was assessed immunohistochemically in tumoral samples of 65 pancreatic adenocarcinoma patients and statistically analyzed in relation to clinicopathological characteristics, tumor proliferative capacity, and patients' survival. RESULTS: Of the 65 adenocarcinoma patients, 49 (75%) tested positive for PPAR-gamma and 55 (85%) stained positive for RXR-alpha. RXR-alpha positivity was significantly associated with tumor proliferative capacity and PPAR-gamma positivity (p=0.022 and p=0.043, respectively). PPAR-gamma and RXR-alpha staining intensity were associated with the histopathological tumor grade (p=0.003 and p=0.038, respectively). Significant associations of PPAR-gamma staining intensity and RXR-alpha expression with tumor size were also noted (p=0.041 and p=0.038, respectively). Moderate and intense PPAR-gamma staining intensity was associated with shorter overall survival in univariate analysis (log-rank test, p=0.023) and proved to be an independent prognostic factor in multivariate analysis (p=0.045), whereas RXR-alpha failed to predict patients' survival. CONCLUSIONS: These data revealed that both PPAR-gamma and RXR-alpha were associated with pancreatic cancer characteristics. PPAR-gamma, but not RXR-alpha, was found to be an independent prognostic indicator. However, further molecular and clinical studies are required to delineate the potential clinical application of PPAR-gamma and RXR-alpha in the prognosis and management of pancreatic adenocarcinoma patients.
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