Expression analysis of genes involved in ovarian cancer metastasis.

5038 Background: Epithelial ovarian cancer is the most lethal gynecologic malignancy. Patients with early stage ovarian cancer have an excellent prognosis, in contrast to patients with advanced stage disease, who have a 5-year survival of less than 30%. Although the transition from early to advanced stage disease is a critical determinant of survival, little is known about the molecular genetics that underlie metastasis. The purpose of this study was to evaluate the role of 5 genes previously implicated in human carcinogenesis (FABP4, P53, CCL19, FHL2, POLYDOM), in ovarian cancer metastasis. METHODS: Expression levels of the FABP4, P53, CCL19, FHL2, and POLYDOM genes were measured using quantitative real time polymerase chain reaction (QRTPCR) in 39 ovarian cancer samples collected from primary and metastatic sites from 14 patients undergoing primary surgical cytoreduction for advanced stage (IIIC/IV) serous epithelial ovarian cancer. Twenty-five samples were resected from the left and/or right ovary and 14 samples from the omentum. All samples were subject to QRTPCR analysis in triplicate and mean values reported. Mean expression values were subject to statistical analysis by student's t-test. This study was IRB approved and informed consent obtained. RESULTS: Higher expression was identified in omental metastases compared to primary ovarian specimens in the CCL19 (7.8-fold), FABP4 (5.2-fold), POLYDOM (2.4-fold), and P53 (1.1-fold) genes. In contrast, FHL-2 gene expression was 1.25-fold higher in primary ovarian samples than matched omental metastasis. CONCLUSION: We have evaluated expression of 5 genes that may contribute to omental metastasis from epithelial ovarian cancer. All 5 genes have functions that are biologically consistent with a role in cancer progression and metastasis. Defining the molecular genetic changes associated with ovarian cancer metastasis identifies targets for novel therapeutic interventions that may improve survival for patients with advanced stage disease. No significant financial relationships to disclose.

Duke Scholars

Author Andrew Berchuck Obstetrics and Gynecology, Gynecologic Oncology