Elevated PDGFRB gene copy number gain is prognostic for improved survival outcomes in resected malignant pleural mesothelioma

PDGF/PDGFR pathway has been implicated in malignant pleural mesothelioma (MPM) carcinogenesis; and evidence suggests autocrine mechanisms of proliferation. We sought to evaluate the incidence of PDGFR beta gene copy number gain (CNG) by fluorescence in situ hybridization and PDGFR pathway protein expression by immunohistochemistry (IHC) and correlate it to patient clinical outcome. Eighty-eight archived tumor blocks from resected MPM with full clinical information were used to perform IHC biomarkers (PDGFR alpha, PDGFR beta, p-PDGFR beta) and fluorescence in situ hybridization analysis of PDGFR beta gene CNG. Spearman rank correlation, Wilcoxon rank-sum test, Kruskal-Wallis test, BLiP plots, and Kaplan-Meier method were used to analyze the biomarkers and correlation to clinical outcome. Several correlations between the IHC biomarkers were seen; however, none correlated to clinically relevant patient demographics or histology. In the CNG analysis, PDGFR beta gene CNG in >10% of tumor cells had lower cytoplasmic p-PDGFR beta (P = .029), while PDGFR beta gene CNG in >40% of tumor cells had a higher cytoplasmic PDGFR beta (P = .04). PDGFR beta gene CNG status did not associate with patient demographics or tumor characteristics. PDGFR pathway IHC biomarkers did not associate with survival outcomes. However, patients with PDGFR beta CNG >40% of tumor cells had improved relapse-free survival (HR 0.25 [95% CI 0.09-0.72], P = .0096) and improved overall survival (HR 0.32 [95% CI 0.11-0.89], P = .029). PDGFR beta CNG >40% of MPM tumor cells is a potential prognostic biomarker for surgery and may identify a unique population of mesothelioma patients. Future validation of this biomarker in prospective trials is needed. From a retrospective review of archived tissue specimens from patients with resected malignant pleural mesothelioma tumors, we show that patients with PDGFR beta CNG >40% of tumor cells had improved relapse-free survival (HR 0.25 [95% CI 0.09-0.72], P = .0096) and improved overall survival (HR 032 [95% CI 0.11-0.89], P = .029). PDGFR beta CNG >40% of MPM tumor cells is a potential prognostic biomarker for surgery and may identify a unique population of mesothelioma patients. (C) 2014 Elsevier Inc. All rights reserved.