Sustained expression of steroid receptor coactivator SRC-2/TIF-2 is associated with better prognosis in malignant pleural mesothelioma.
Authors
Jennings, Cormac JO'Grady, Anthony
Cummins, Robert
Murer, Bruno
Al-Alawi, Mazen
Madden, Stephen F
Mutti, Luciano
Harvey, Brian J
Thomas, Warren
Kay, Elaine W
Affiliation
Department of Molecular Medicine, Royal College of Surgeons in Ireland, Education, and Research Centre, Beaumont Hospital, Dublin, Ireland.Issue Date
2012-02-01T10:04:32Z
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J Thorac Oncol. 2012 Jan;7(1):243-8.Journal
Journal of thoracic oncology : official publication of the International, Association for the Study of Lung CancerDOI
10.1097/JTO.0b013e31822f6544PubMed ID
22011668Abstract
INTRODUCTION: Estrogen receptor beta (ERbeta) 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 ERbeta. Allred scores for expression of ERbeta 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: ERbeta 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.Language
engISSN
1556-1380 (Electronic)1556-0864 (Linking)
ae974a485f413a2113503eed53cd6c53
10.1097/JTO.0b013e31822f6544
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