Abstract 687: Enhanced expression of multidrug resistance (MDR) protein in malignant pleural mesothelioma (MPM) patients is possibly achieved via Osteoponin, CD44 variants and p-AKT expression

Abstract

Abstract Malignant pleural mesothelioma (MPM) is an aggressive disease, which is discovered late. It is resistant to chemotherapy and thus shows a dismal prognosis. Recently, in vitro studies demonstrated that osteoponin (is involved in the development of MPM via induction of multidrug resistance through unidentified mechanism(s). Tissue and serum samples from 55 Egyptian cases of MPM were assessed for OPN, MDR, p-AKT and CD44 proteins and RNA by ELISA, immunohistochemistry (IHC) and RT-PCR. Normal pleural samples (20) were used as a control. Results were correlated with standard prognostic factors and survival. In tissues, OPN, CD44, MDR and p-AKT protein overexpression was detected in 39, 26, 37 and 25 cases; respectively whereas RNA expression was reported in 31, 24, 30, 24 cases; respectively. In sera, OPN, CD44, MDR and p-AKT proteins were found in 36, 20, 40, 28 cases; respectively. There was a significant correlation between OPN expression and other markers, at the protein and RNA levels (p<0.05). The concordance between OPN and MDR expression was the highest (98%). Control samples were negative for the studied markers except for 4 cases that showed faint focal expression of p-AKT and CD44 proteins. OS was significantly associated with performance status, increased expression of OPN, MDR and CD44 in univariate and multivariate analysis (p<0.01). A borderline significance was reported between poor response to treatment and increased expression of OPN, CD44, MDR either singly (p=0.063) or combined (p=0.045) In conclusion, OPN, CD44, and p-AKT could be used as poor prognostic markers in MPM being associated with reduced OS rates and poor response to treatment. This could be achieved via enhanced MDR expression with subsequent resistance to chemotherapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 687. doi:10.1158/1538-7445.AM2011-687