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

Our plain-English summary of Sustained expression of steroid receptor coactivator SRC-2/TIF-2 is associated with better prognosis in malignant pleural mesothelioma, by C.J. Jennings, A. O'Grady, R. Cummins, et al (Journal of Thoracic Oncology, 2012).

The study

• Authors: C.J. Jennings, A. O'Grady, R. Cummins, B. Murer, M. Al-Alawi, S.F. Madden, L. Mutti, B.J. Harvey, W. Thomas, E.W. Kay
• Journal: Journal of Thoracic Oncology
• Published: 2012;7(1):243-8
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

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.

In plain English

This study examined archived tumor tissue from 89 people with malignant pleural mesothelioma at the Regional Hospital of Mestre-Venice, Italy, plus normal pleura from 3 control subjects. The study did not look at asbestos exposure. The authors stained the samples for three related proteins called steroid receptor coactivators (SRC-1, TIF-2 and AIB-1) and for estrogen receptor beta. They then compared protein levels with how long patients lived after diagnosis. All of these markers were strongly present in normal pleura and were reduced or absent in some tumors. Patients whose tumors had high TIF-2 had a median survival of 20 months, compared with 9 months for those with low or intermediate TIF-2 (p = 0.036). This pattern was also seen among patients with epithelioid tumors (23 versus 9 months) and among men (20 versus 8 months). After adjustment for gender, age, tumor type and chemotherapy, the hazard ratio for high versus low or intermediate TIF-2 was 0.526 (95% confidence interval 0.301 to 0.918). For estrogen receptor beta, median survival was 15 versus 8 months, which was not statistically significant. The authors concluded that maintained high TIF-2 in tumor cells is a positive prognostic indicator for survival after diagnosis.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective laboratory study of archived tumor biopsies, using immunohistochemical staining and survival analysis (Kaplan-Meier curves, log-rank tests, multivariate Cox regression)
• Who was studied: 89 patients with confirmed malignant pleural mesothelioma (73 male, 16 female; ages 44 to 82; 71 epithelioid, 10 biphasic, 8 sarcomatoid) and 3 normal control subjects, identified from archival pathology files of the Regional Hospital of Mestre-Venice, Italy, with more than 5 years of follow-up after diagnosis; calendar dates not given
• Exposure: Asbestos exposure was not studied. The factors examined were tumor levels of the steroid receptor coactivators SRC-1, TIF-2 (SRC-2) and AIB-1 (SRC-3), and of estrogen receptor beta, scored with the Allred system (6 or greater counted as high/strong staining)
• Main results:
  • All three normal pleura samples stained with high intensity for estrogen receptor beta and each of the coactivators
  • High TIF-2 staining was found in 38 of 89 patients (42.7%); low or intermediate staining was found in 51 (57.3%)
  • Whole cohort: median survival after diagnosis was 20 months with high TIF-2 versus 9 months with low or intermediate TIF-2 (p = 0.036, log-rank test)
  • Epithelioid tumors only (n = 71): median survival was 23 months with high TIF-2 versus 9 months with low or intermediate TIF-2 (reported p value 0.031)
  • Men only (n = 73): median survival was 20 months with high TIF-2 versus 8 months with low or intermediate TIF-2 (reported p value 0.003)
  • Adjusted for gender, age at diagnosis, histological type and chemotherapy, the hazard ratio for high versus low or intermediate TIF-2 was 0.526 (95% CI 0.301 to 0.918), p 0.0239 (two-sided Wald test)
  • For other markers: SRC-1 high versus intermediate/low, median survival 14 versus 10 months; AIB-1, 12 months in both groups; estrogen receptor beta positive versus negative, 15 versus 8 months, not statistically significant (p 0.254)
  • Median survival was 18 months for women and 10 months for men, a difference that was not statistically significant in this cohort (p 0.101)
• The authors' conclusion: The authors concluded that maintained high TIF-2 expression in tumor cells is a positive prognostic indicator for survival after diagnosis in patients with confirmed malignant pleural mesothelioma, and described this as the first clinical study to link high TIF-2 with better prognosis in any cancer

Topics

The National Library of Medicine indexes this study under subjects our site covers: Mesothelioma.

Medical terms in this study, explained in our Lexicon: Prognosis, Pleural Mesothelioma, Biomarker, Histology, Mesothelium.

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