Expression of Wilms' tumor gene (WT1) is associated with survival in malignant pleural mesothelioma

Our plain-English summary of Expression of Wilms' tumor gene (WT1) is associated with survival in malignant pleural mesothelioma, by S. Cedrés, M.A. Montero, E. Zamora, et al (Clinical & Translational Oncology, 2014).

The study

• Authors: S. Cedrés, M.A. Montero, E. Zamora, A. Martínez, P. Martínez, L. Fariñas, A. Navarro, D. Torrejon, A. Gabaldon, S. Ramon Y Cajal, E. Felip
• Journal: Clinical & Translational Oncology
• Published: 2014;16(9):776-82
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Introduction: Calretinin and Wilms' tumor gene (WT1) are mesothelial markers routinely used to confirm the diagnosis of malignant pleural mesothelioma (MPM). We investigated the prognostic value of calretinin and WT1 expression in predicting survival in a series of patients diagnosed with MPM in our institution.

Materials And Methods: Fifty-two patients diagnosed of MPM were retrospectively reviewed. Calretinin and WT1 were stained for IHC analysis in formalin-fixed, paraffin-embedded sections and positivity was considered for tumors with >1 % of tumor cells stained. Survival data were calculated by the Kaplan-Meier method and Cox regression was used to evaluate the prognostic value of the variables.

Results: Calretinin IHC expression was positive in 83.7 % of patients and WT1 in 78.1 %. A significant association of calretinin and WT1 expression with epithelial histology was detected (p = 0.030 and p = 0.010). We found a significant increase in OS in patients with epithelial subtype, PS1 and neutrophil-lymphocyte ratio (NLR) ≤5 (p < 0.05). In the IHC markers analysis, we found a significant increase in OS for patients with WT1 positive expression (16.4 vs. 2.3 m, p = 0.013), but not differences for calretinin expression (16.6 vs. 5.0 months, p = 0.37). In the multivariate analysis, epithelial histology and WT1 remained as significant prognostic factors for survival (p = 0.004 and p = 0.010, respectively).

Conclusion: In our series of 52 MPM patients, epithelial histology, PS, NLR and WT1 expression are significant prognostic factors for survival. We concluded that WT1, but not calretinin, is a useful prognostic factor in MPM. The role of WT1 assessment is worth of prospective validation in future studies on MPM.

In plain English

This retrospective study looked at 52 consecutive patients with malignant pleural mesothelioma collected from 2002 to 2011 at Vall d'Hebron University Hospital in Barcelona. The authors stained tumor biopsy samples for two markers used to confirm the diagnosis, calretinin and WT1 (Wilms' tumor gene), and tested whether they were linked to survival. Calretinin was positive in 41 of 47 patients tested and WT1 in 25 of 32. The patient table listed asbestos exposure for 28 patients. Median survival for the whole group was 15.2 months (95% confidence interval 7.41 to 23.01 months). Patients with WT1-positive tumors had longer overall survival than those with WT1-negative tumors (16.36 versus 2.33 months), a statistically significant difference. The calretinin difference (16.4 versus 5.0 months) was not statistically significant. In the combined analysis, epithelial tumor type and WT1 remained significant. The authors concluded that WT1, but not calretinin, is a useful prognostic factor. They noted that the study was retrospective and small and needs confirmation in another group of patients, preferably followed forward in time.

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 review of consecutive cases, with immunohistochemical staining of tumor samples and survival analysis
• Who was studied: 52 patients with malignant pleural mesothelioma at Vall d'Hebron University Hospital, Barcelona, 2002 to 2011: 37 epithelioid, 12 biphasic and 3 sarcomatoid. Median age was 68. None had surgery and 38 received chemotherapy. WT1 results were available for 32 samples and calretinin results for 47.
• Exposure: The factors studied were calretinin and WT1 staining in tumor tissue, counted as positive if more than 1% of tumor cells stained. Table 1 lists asbestos exposure for 28 patients (53.1%). No fiber types, products or jobs are given.
• Main results:
  • Median survival for the whole group of 52 patients was 15.2 months (95% CI 7.41 to 23.01).
  • Calretinin was positive in 41 of 47 patients evaluated (printed as 83.7%). WT1 was positive in 25 of 32 patients (78.1%).
  • Patients with WT1-positive tumors had longer overall survival than those with WT1-negative tumors: 16.36 vs. 2.33 months, p = 0.013.
  • Survival for calretinin-positive versus calretinin-negative patients (median 16.4 vs. 5.0 months) was not statistically significantly different (p = 0.37).
  • Longer survival was seen for patients with epithelial subtype (23.4 vs. 5.0 months), low neutrophil-to-lymphocyte ratio (26.45 vs. 13.38 months, p = 0.025) and performance status 1 vs. 2 (14.7 vs. 2.33 months, p = 0.036).
  • In the multivariate Cox analysis, epithelial histology (HR 22.85, CI 2.74 to 190.65, p = 0.004) and WT1 (HR 9.58, CI 1.76 to 52.31, p = 0.009) remained significant. Calretinin and NLR did not.
  • WT1 expression was significantly associated with epithelial histology (p = 0.010). Calretinin expression was also associated with epithelial histology (p = 0.027).
• The authors' conclusion: The authors concluded that WT1, but not calretinin, is a useful prognostic factor in malignant pleural mesothelioma, and that WT1 assessment deserves prospective validation.
• Limitations the authors state:
  • The study was retrospective, with the problems inherent to retrospective analysis.
  • The number of patients was small.
  • Positivity was defined as more than 1% of tumor cells stained, without stratifying by staining intensity.
  • The results need validation in an independent series, preferably prospective.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Calretinin, Histology, Multivariate Analysis.

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