Mesothelioma, Steroid Receptor Co-Activator, Estrogen Receptor
Health Re-search Board (Ireland), by the Higher Education Authority(Ireland) through the National Biophotonics and Imaging Platform; and by a Science Foundation Ireland, Strategic Research Cluster award to Molecular Therapeutics for Cancer Ireland (award 08/SRC/B1410).
INTRODUCTION: Estrogen receptor beta (ERβ) overexpression by malignant pleural mesothelioma (MPM) tumor cells correlates with enhanced patient survival. ER-regulated transcription is mediated by the p160 family of steroid receptor coactivators (SRCs), and SRC isoform overexpression is associated with worse prognosis in many steroid-related malignancies. The aim of this study was to establish whether SRC isoform expression varied between individual MPM tumors with positive or negative prognostic significance.
METHODS: Immunohistochemical analysis of tumor biopsies from 89 subjects with confirmed histological diagnosis of MPM and biopsies from 3 normal control subjects was performed to detect the expression of SRC-1, SRC-2 (TIF-2), SRC-3 (AIB-1), and ERβ. Allred scores for expression of ERβ and each of the SRCs were determined, and Kaplan-Meier survival curves were calculated to correlate biomarker expression, gender, and histology type with postdiagnosis survival.
RESULTS: ERβ and all the SRCs were expressed at high levels in normal pleural mesothelium, and expression of each biomarker was reduced or lost in a subset of the MPM subjects; however, postdiagnosis survival only significantly correlated with TIF-2 expression. Low or intermediate expression of TIF-2 correlated with reduced median postdiagnosis survival (9 months) compared with those subjects whose tumors highly expressed TIF-2 (20 months) (p = 0.036, log-rank test).
CONCLUSIONS: Maintained high expression of TIF-2 in tumor cells is a positive prognostic indicator for postdiagnosis survival in patients with confirmed MPM. This is the first clinical study to correlate high TIF-2 expression with improved patient prognosis in any malignancy.
Medical Molecular Biology | Medical Sciences
Jennings C, O'Grady A, Cummins R, Murer B, Al-Alawi M, Madden SF, Mutti L. Harvey BJ, Thomas W, Kay EW. Sustained Expression of Steroid Receptor Coactivator SRC-2/TIF-2 is Associated with Better Prognosis in Malignant Pleural Mesothelioma. Journal of Thoracic Oncology. 2012;7(1):243-8.
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