Expression of the peroxisome proliferator-activated receptors-alpha, -beta, and -gamma in ovarian carcinoma effusions is associated with poor chemoresponse and shorter survival.
Peroxisome 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-alpha, -beta, and -gamma messenger RNA expression using reverse transcriptase polymerase chain reaction. Peroxisome proliferator-activated receptor-gamma messenger RNA expression was further assessed in 60 tumors (30 effusions, 20 primary carcinomas, 10 metastases) using in situ hybridization. Peroxisome proliferator-activated receptor-gamma 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-alpha (P = .004) and peroxisome proliferator-activated receptor-beta (P = .002) messenger RNA levels were higher in effusions compared with primary carcinomas and solid metastases. In situ hybridization localized peroxisome proliferator-activated receptor-gamma messenger RNA to carcinoma cells in both effusions and solid lesions. Peroxisome proliferator-activated receptor-gamma 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-gamma 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.
Davidson
Ben
B
Division of Pathology, Norwegian Radium Hospital, Rikshospitalet Medical Center, Montebello N-0310, Oslo, Norway. ben.davidson@radiumhospitalet.no
Hadar
Rivka
R
Stavnes
Helene Tuft
HT
Trope'
Claes G
CG
Reich
Reuven
R
D000328:Adult; D000368:Aged; D016824:Antigens, Human Platelet / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001202:Ascitic Fluid; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D047493:PPAR alpha / Q000096:biosynthesis*; D047495:PPAR gamma / Q000096:biosynthesis*; D048068:PPAR-beta / Q000096:biosynthesis*; D016066:Pleural Effusion, Malignant; D011379:Prognosis; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
D016824:Antigens, Human Platelet; D000970:Antineoplastic Agents; D047493:PPAR alpha; D047495:PPAR gamma; D048068:PPAR-beta; D012333:RNA, Messenger; C083451:human platelet antigen 1b