Nuclear expression of CXCR4 is an independent prognostic factor for overall and progression-free survival in malignant pleural mesothelioma

Abstract

7196 Background: CXCR4 is a chemokine receptor which takes part in diverse events like the migration of lymphocytes to sites of inflammation, internalization of the HIV particle by lymphocytes, and homing of metastasizing tumor cells. Recent studies suggest that nuclear -rather than membranous or cytoplasmic- expression of CXCR4 may signify a different function. In this study, we aimed to evaluate the prognostic significance of nuclear CXCR4 expression in patients with malignant pleural mesothelioma (MPM). Methods: The records of 66 MPM patients were reviewed and CXCR4 expression of their tumors were assessed by immunohistochemistry. Prognostic significance of this marker was evaluated using Log rank test and a Cox proportional hazards model. Results: The mean age of patients was 61±10 years (min: 41, max: 85). Fifty-one patients were males (77%), and 15 were females (23%). The median percentage of cells expressing nuclear CXCR4 was 5.1% (min-max: 0–95), and this was used as the cut-off to define CXCR4-positive and negative tumors. Patients whose tumor expressed nuclear CXCR4 had a median overall survival (OS) of 20.9 months (95% confidence interval [CI]: 11.8–30.0) while those with negative tumors had an OS of 11.9 mths (95% CI: 11.3–12.5; p=0.03). Similarly, median progression-free survival (PFS) was 13.6 mths (95% CI: 9.2–18.0) and 7.4 mths (95% CI: 4.6–10.3) for CXCR4-positive and negative cases, respectively (p=0.02). A multivariate model including other possible prognostic factors like age, sex, stage and histological subtype showed that nuclear CXCR4 expression is an independent prognostic factor, both for OS and PFS (p=0.01 and p=0.005, respectively). Conclusions: Nuclear expression of CXCR4 is associated with better OS and PFS in patients with MPM. The mechanisms underlying the favorable impact of the aberrant localization of this molecule merits further investigation. No significant financial relationships to disclose.