RGD Reference Report - Sustained expression of steroid receptor coactivator SRC-2/TIF-2 is associated with better prognosis in malignant pleural mesothelioma. - Rat Genome Database

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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 
Citation: Jennings CJ, etal., J Thorac Oncol. 2012 Jan;7(1):243-8. doi: 10.1097/JTO.0b013e31822f6544.
RGD ID: 153002578
Pubmed: PMID:22011668   (View Abstract at PubMed)
DOI: DOI:10.1097/JTO.0b013e31822f6544   (Journal Full-text)


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.




  
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Original Reference(s)
NCOA2Humanmalignant pleural mesothelioma amelioratesIEP protein:increased expression:mesothelium of pleural cavity (human)RGD 
Ncoa2Ratmalignant pleural mesothelioma amelioratesISONCOA2 (Homo sapiens)protein:increased expression:mesothelium of pleural cavity (human)RGD 
Ncoa2Mousemalignant pleural mesothelioma amelioratesISONCOA2 (Homo sapiens)protein:increased expression:mesothelium of pleural cavity (human)RGD 


Genes (Rattus norvegicus)
Ncoa2  (nuclear receptor coactivator 2)

Genes (Mus musculus)
Ncoa2  (nuclear receptor coactivator 2)

Genes (Homo sapiens)
NCOA2  (nuclear receptor coactivator 2)