CCL2 expression in ovarian carcinoma is associated with chemotherapy response and survival but not with the -2518 A/A polymorphism

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16509 Background: CCL2, a macrophage chemoattractant, is expressed in normal human ovarian epithelium but down-regulated in ovarian adenocarcinomas. The purpose of this study was to determine the association between quantitative expression of CCL2 with chemotherapy response and clinical outcome in ovarian cancer (OC) patients (pts) as well as its association with a known polymorphism (-2518 A/A) in the CCL2 promoter region. Methods: Solid or ascitic tumor cells from pts with advanced papillary serous OC were obtained at the time of primary surgery or neoadjuvant chemotherapy. RT-PCR with PCR-based amplification of the CCL2 promoter region containing the -2518 A/A polymorphism (PM) was performed on samples of genomic DNA from blood and tumor. The PM frequency was compared to the genotype frequency in control patients with renal cell carcinoma (RCC). Chemoresponse was correlated with genotype and CCL2 expression. Sensitive (S) tumors = complete response and no disease recurrence/progression 6 months after treatment. Resistant tumors (R) = progression or recurrence ≤6 months after treatment. Results: Sixty nine pt specimens were analyzed. The incidence of the PM in blood and matched tumor was 65 and 70%, respectively, a frequency significantly higher than that previously reported (∼50%) in population-based studies on CCL2 polymorphisms and higher than that in the RCC group (54%, p =0.02). 46/69 patients had clinical follow up (f/u) data available (median f/u = 36 months). RT-PCR analysis demonstrated that CCL2 was significantly down-regulated in the R versus the S tumors (p<0.001). Sensitivity was 89%. Lack of CCL2 mRNA expression correlated inversely with progression free survival (PFS, p=0.05) and overall survival (OS, p=0.01). Expression of the PM was not predictive of response or survival. On multivariate analysis, only debulking status and CCL2 expression were predictive of PFS and OS. Conclusions: Decreased expression of CCL2 is associated with poorer chemoresponse and survival. Although the CCL2 promoter-region PM -2518 A/A is commonly expressed in women with ovarian carcinoma, it is not predictive of PFS or OS. Further studies are needed to characterize the relationship between this PM, expression of CCL2 and clinical outcomes. No significant financial relationships to disclose.