Molecular predictors for response to carboplatinum and paclitaxel (CP) chemotherapy in patients with ovarian cancer

5066 Backgound: The standard treatment of advanced-stage ovarian cancer includes cytoreductive surgery followed by CP chemotherapy. While this regimen is effective, emergence of resistance hinders successful outcomes. Our goal was to improve patient selection for this specific chemotherapy and develop strategies to overcome resistance by determining the molecular mechanisms associated with it. Methods: A tissue array composed of 40 advanced-stage ovarian cancer patients treated with surgery followed by CP chemotherapy has been constructed; clinical data are available. We measured protein expression levels of pro-apoptotic (p53, p27) and anti-apoptotic (c-MET, phospho-Akt) factors using conventional immunohistochemistry (IHC) and/or a novel method of in-situ quantitative analysis of protein expression. The results were analyzed with Mantel-Haenszel Chi-Square test. Results: Low p27 levels (p=0.005) and serous histology (0.016) were associated with chemosensitivity. p53, phosho-Akt and cMET did not correlate with sensitivity. Conclusions: Our results are consistent with reports implicating p27KIP1 as a mediator of adhesion-dependent drug resistance; cell-cell interactions may signal the upregulation of p27, which in turn causes growth arrest in the G1 phase of the cell cycle and resistance to apoptosis induced by anticancer agents targeting rapidly dividing cells. These results need to be confirmed; a tissue array composed of 300 advanced ovarian cancer cases treated with CP is being constructed and will be used to test this finding. No significant financial relationships to disclose.