Clinical significance of epithelial-mesenchymal transition-associated markers in malignant pleural mesothelioma

Our plain-English summary of Clinical significance of epithelial-mesenchymal transition-associated markers in malignant pleural mesothelioma, by T. Iwanami, H. Uramoto, M. Nakagawa, et al (Oncology, 2014).

The study

• Authors: T. Iwanami, H. Uramoto, M. Nakagawa, H. Shimokawa, S. Yamada, K. Kohno, F. Tanaka
• Journal: Oncology
• Published: 2014;86(2):109-16
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Epithelioid tumors with aggressive behavior have been reported; however, the epithelioid type of malignant pleural mesothelioma (MPM) has a less aggressive behavior. Few studies have evaluated the prognostic value of epithelial-mesenchymal transition (EMT) markers in MPM. We hypothesized that mesenchymal characteristics might predominate in the tumors. Tumor specimens were collected from 33 consecutive patients. We analyzed the EMT expression levels in tumor samples by an immunohistochemical analysis. Positive expression of E-cadherin, γ-catenin, vimentin, fibronectin, Twist and YB-1 was observed in 25, 14, 21, 1, 19 and 18 patients, respectively. No significant association between these markers and the clinicopathological characteristics was found. γ-Catenin demonstrated a trend towards decreased expression in sarcomatoid tumors compared to epithelioid tumors. On the other hand, a trend was noted towards higher expression of vimentin, Twist and YB-1 in sarcomatoid tumors. The survival curves demonstrated that the patients with negative γ-catenin and positive Twist staining had a tendency to have a worse prognosis. Although the individual proteins might not significantly affect the progression of MPM, the combination of γ-catenin and Twist staining can predict the prognosis of patients with MPM.

© 2014 S. Karger AG, Basel.

In plain English

This retrospective, single-institution study from Japan examined tumor tissue from 33 patients operated on for malignant pleural mesothelioma between 1998 and 2012 (17 epithelioid, 10 biphasic, 6 sarcomatoid). Asbestos exposure was noted in 21 cases; asbestos itself was not analyzed. The authors stained tumors for six markers of epithelial-mesenchymal transition, in which epithelial cells change into mesenchymal-like cells. Staining was positive in 25 patients for E-cadherin, 14 for γ-catenin, 21 for vimentin, 1 for fibronectin, 19 for Twist and 18 for YB-1. Twist was positive in all 6 sarcomatoid versus 7 of 17 epithelioid tumors (p = 0.013). No single marker showed a statistically significant survival difference. Patients with negative γ-catenin and positive Twist tended toward worse survival (p = 0.061), significantly so among epithelioid tumors only (p = 0.035). In multivariate analysis this combination's relative risk was 3.482 (95% CI 0.948 to 8.711), which the authors called a marginal association. The authors concluded the combination could predict prognosis, while stating that the small number of patients precludes firm conclusions.

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, single-institution study of tumor tissue using immunohistochemical staining, with survival analysis
• Who was studied: Tumor samples from 38 Japanese patients who had surgery for malignant pleural mesothelioma between 1998 and 2012 at the authors' department (University of Occupational and Environmental Health, Kitakyushu, Japan). Samples from 5 patients were too small, leaving 33 evaluated: 31 males and 2 females, mean age 66.5 years (range 51 to 85). Tumor types: 17 epithelioid, 10 biphasic, 6 sarcomatoid.
• Exposure: Asbestos exposure was noted in 21 of the 33 cases. Fiber types, sources and doses were not reported. The study measured six epithelial-mesenchymal transition markers in tumor tissue (E-cadherin, γ-catenin, vimentin, fibronectin, Twist, YB-1). It did not analyze asbestos exposure.
• Main results:
  • Of the 33 patients, positive staining was seen in 25 for E-cadherin, 14 for γ-catenin, 21 for vimentin, 1 for fibronectin, 19 for Twist and 18 for YB-1.
  • Twist was positive in 7 of 17 epithelioid, 6 of 10 biphasic and 6 of 6 sarcomatoid tumors. The difference between sarcomatoid and epithelioid tumors was significant (p = 0.013). It was the only marker that differed significantly by tumor type.
  • γ-catenin tended to be lower in sarcomatoid tumors (1 of 6) than in epithelioid tumors (9 of 17). This difference was not statistically significant (p = 0.136).
  • In all patients, no individual marker was linked to a statistically significant difference in survival.
  • Among all patients, those with negative γ-catenin and positive Twist staining tended toward worse survival. This was not statistically significant (p = 0.061).
  • Among patients with epithelioid tumors only, the survival difference for negative γ-catenin plus positive Twist was statistically significant (p = 0.035).
  • In the multivariate analysis, negative γ-catenin plus positive Twist had a relative risk of death of 3.482 (95% CI 0.948 to 8.711, p = 0.062; Table 2). The authors described this as a marginal association.
• The authors' conclusion: The authors concluded that individual markers might not contribute to the progression of malignant pleural mesothelioma. They concluded that a combination of γ-catenin and Twist could be used to predict prognosis, and that further research is needed.
• Limitations the authors state:
  • The study was retrospective and carried out at a single institution.
  • The patients did not all receive the same treatment.
  • The six markers studied do not reflect the whole epithelial-mesenchymal transition process.
  • The small number of patients precludes firm conclusions; the authors describe the results as hypothesis generating.
  • Imbalances in patient characteristics cannot be ruled out because of the small number of patients.

Topics

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

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Epithelioid, Sarcomatoid, Prognosis.

Related studies

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• Epithelial to Mesenchymal Transition in Human Mesothelial Cells Exposed to Asbestos Fibers: Role of TGF-β as Mediator of Malignant Mesothelioma Development or Metastasis via EMT Event — S. Turini, L. Bergandi, et al. (2019)
• Prognostic significance of epithelial-mesenchymal transition in malignant pleural mesothelioma — A. Schramm, I. Opitz, et al. (2010)
• Expression of snail, twist, and Zeb1 in malignant mesothelioma — H. Merikallio, P. Pääkkö, et al. (2013)
• Epithelial-mesenchymal transition in malignant mesothelioma — A. Fassina, R. Cappellesso, et al. (2012)
• The Epithelial-to-Mesenchymal Transition (EMT) in the Development and Metastasis of Malignant Pleural Mesothelioma — V. Ramundo, G. Zanirato, et al. (2021)

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