Expression of the peroxisome proliferator–activated receptors–α, –β, and –γ in ovarian carcinoma effusions is associated with poor chemoresponse and shorter survival

SummaryPeroxisome proliferator–activated receptors regulate lipid metabolism, affecting inflammation and cancer. The present study analyzed the anatomical site–related expression and prognostic role of peroxisome proliferator–activated receptors in ovarian carcinoma. Fresh-frozen effusions (n = 79), primary carcinomas (n = 44), and solid metastases (n = 16) were studied for peroxisome proliferator–activated receptor–α, –β, and –γ messenger RNA expression using reverse transcriptase polymerase chain reaction. Peroxisome proliferator–activated receptor–γ messenger RNA expression was further assessed in 60 tumors (30 effusions, 20 primary carcinomas, 10 metastases) using in situ hybridization. Peroxisome proliferator–activated receptor–γ protein expression was immunohistochemically analyzed in 160 effusions. All peroxisome proliferator–activated receptors were expressed in most tumors at all anatomical sites using reverse transcriptase polymerase chain reaction, but peroxisome proliferator–activated receptor–α (P = .004) and peroxisome proliferator–activated receptor–β (P = .002) messenger RNA levels were higher in effusions compared with primary carcinomas and solid metastases. In situ hybridization localized peroxisome proliferator–activated receptor–γ messenger RNA to carcinoma cells in both effusions and solid lesions. Peroxisome proliferator–activated receptor–γ protein was detected in carcinoma cells in 102 of 160 (64%) effusions. Higher effusion messenger RNA levels of all peroxisome proliferator–activated receptors were associated with less favorable response to chemotherapy at diagnosis (P = .009). In univariate survival analysis, higher messenger RNA expression of all peroxisome proliferator–activated receptors was associated with poor progression-free (P = .045) and overall (P = .014) survival. Higher peroxisome proliferator–activated receptor–γ protein expression was similarly associated with poor overall survival for the entire cohort (P = .046) and for patients with disease recurrence effusions (P = .009). Peroxisome proliferator–activated receptors were not independent predictors of survival in Cox multivariate analysis. Peroxisome proliferator–activated receptor members are frequently expressed in ovarian carcinoma, with upregulated expression in effusions. Peroxisome proliferator–activated receptor expression in effusions is associated with poor response to chemotherapy at disease recurrence and poor survival, suggesting a role in tumor biology at this unique microenvironment.