Sustained Expression of Steroid Receptor Coactivator SRC-2/TIF-2 is Associated with Better Prognosis in Malignant Pleural Mesothelioma

• Published in: Journal of thoracic oncology Vol. 7; no. 1; pp. 243 - 248
• Main Authors: Jennings, Cormac J., O'Grady, Anthony, Cummins, Robert, Murer, Bruno, Al-Alawi, Mazen, Madden, Stephen F., Mutti, Luciano, Harvey, Brian J., Thomas, Warren, Kay, Elaine W.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2012; International Association for the Study of Lung Cancer
• Subjects: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - metabolism; Biopsy; Estrogen receptor; Estrogen Receptor beta - metabolism; Female; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Mesothelioma; Mesothelioma - metabolism; Mesothelioma - pathology; Middle Aged; Nuclear Receptor Coactivator 1 - metabolism; Nuclear Receptor Coactivator 2 - metabolism; Nuclear Receptor Coactivator 3 - metabolism; Pleura - pathology; Pleural Neoplasms - metabolism; Pleural Neoplasms - pathology; Prognosis; Proportional Hazards Models; Sex Factors; Steroid receptor coactivator; Estrogen receptor; Mesothelioma; Steroid receptor coactivator
• ISSN: 1556-0864; 1556-1380; 1556-1380
• DOI: 10.1097/JTO.0b013e31822f6544

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. 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. 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). 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.