Sustained expression of steroid receptor coactivator SRC-2/TIF-2 is associated with better prognosis in malignant pleural mesothelioma.

Hdl Handle:
http://hdl.handle.net/10147/207310
Title:
Sustained expression of steroid receptor coactivator SRC-2/TIF-2 is associated with better prognosis in malignant pleural mesothelioma.
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
Affiliation:
Department of Molecular Medicine, Royal College of Surgeons in Ireland, Education, and Research Centre, Beaumont Hospital, Dublin, Ireland.
Citation:
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 Cancer
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207310
DOI:
10.1097/JTO.0b013e31822f6544
PubMed ID:
22011668
Abstract:
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:
eng
ISSN:
1556-1380 (Electronic); 1556-0864 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorJennings, Cormac Jen_GB
dc.contributor.authorO'Grady, Anthonyen_GB
dc.contributor.authorCummins, Roberten_GB
dc.contributor.authorMurer, Brunoen_GB
dc.contributor.authorAl-Alawi, Mazenen_GB
dc.contributor.authorMadden, Stephen Fen_GB
dc.contributor.authorMutti, Lucianoen_GB
dc.contributor.authorHarvey, Brian Jen_GB
dc.contributor.authorThomas, Warrenen_GB
dc.contributor.authorKay, Elaine Wen_GB
dc.date.accessioned2012-02-01T10:04:32Z-
dc.date.available2012-02-01T10:04:32Z-
dc.date.issued2012-02-01T10:04:32Z-
dc.identifier.citationJ Thorac Oncol. 2012 Jan;7(1):243-8.en_GB
dc.identifier.issn1556-1380 (Electronic)en_GB
dc.identifier.issn1556-0864 (Linking)en_GB
dc.identifier.pmid22011668en_GB
dc.identifier.doi10.1097/JTO.0b013e31822f6544en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207310-
dc.description.abstractINTRODUCTION: 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.en_GB
dc.language.isoengen_GB
dc.titleSustained expression of steroid receptor coactivator SRC-2/TIF-2 is associated with better prognosis in malignant pleural mesothelioma.en_GB
dc.contributor.departmentDepartment of Molecular Medicine, Royal College of Surgeons in Ireland, Education, and Research Centre, Beaumont Hospital, Dublin, Ireland.en_GB
dc.identifier.journalJournal of thoracic oncology : official publication of the International, Association for the Study of Lung Canceren_GB
dc.description.provinceLeinster-

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