Abstract 2688: The expression of lung resistance protein (LRP) in patient ascites predicts platinum resistance in advanced epithelial ovarian carcinoma

Abstract

Abstract The human lung resistance protein (LRP) is a multidrug resistance protein that has been shown to be overexpressed in numerous chemotherapy resistance models. The precise role of LRP in platinum-resistant epithelial ovarian cancer (EOC) has yet to be fully elucidated. In this study, we sought to determine LRP expression in the tumor cells of ovarian cancer patient ascites of chemotherapy-naïve patients with advanced EOC. After IRB approval was obtained, patient ascites was collected and evaluated for platinum sensitivity, and LRP expression using western blot and immunohistochemistry (IHC). Both patient ascites and primary tumor were treated with 50 uM carboplatin for 48h and cell viability was analyzed. LRP, activated Caspase 3, and tunnel were analyzed using IHC on samples treated with 50uM carboplatin and untreated. A total of 27 patients with advanced-stage EOC undergoing primary cytoreductive surgery at the University of Alabama at Birmingham were consented for the study. Ten patient ascites samples were deemed adequate for analysis. Of these, 3/10 (30%) had increased LRP levels in ascites samples demonstrated by strong IHC staining with capping and confirmed by western blot. These patient samples were platinum resistant as verified by cytotoxicity analysis. Two ascites specimens (20%) lacked LRP expression by IHC and western blot and demonstrated platinum sensitivity on cytotoxicity. Five ascites specimens (50%) displayed intermediate LRP staining and platinum cytotoxicity. Tumor cells in ascites treated with carboplatin had an inverse correlation of LRP staining and activated Caspase 3. There is a strong correlation between LRP expression in the ascites of patients with advanced EOC and platinum resistance in this ex vivo model. This protein may therefore predict poor prognosis disease unlikely to respond to adjuvant platinum therapy. Specifically targeting the LRP in a clinical model may reverse carboplatin resistance. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2688.