TY - JOUR
T1 - Expression of the peroxisome proliferator-activated receptors-α, -β, and -γ in ovarian carcinoma effusions is associated with poor chemoresponse and shorter survival
AU - Davidson, Ben
AU - Hadar, Rivka
AU - Stavnes, Helene Tuft
AU - Trope', Claes G.
AU - Reich, Reuven
PY - 2009/5
Y1 - 2009/5
N2 - 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-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.
AB - 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-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.
KW - Chemotherapy
KW - Ovarian carcinoma
KW - PPAR
KW - Serous effusions
KW - Survival
UR - http://www.scopus.com/inward/record.url?scp=64449086798&partnerID=8YFLogxK
U2 - 10.1016/j.humpath.2008.09.019
DO - 10.1016/j.humpath.2008.09.019
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C2 - 19157507
AN - SCOPUS:64449086798
SN - 0046-8177
VL - 40
SP - 705
EP - 713
JO - Human Pathology
JF - Human Pathology
IS - 5
ER -