The established and future biomarkers of malignant pleural mesothelioma

Our plain-English summary of The established and future biomarkers of malignant pleural mesothelioma, by V. Panou, M. Vyberg, U.M. Weinreich, et al (Cancer Treatment Reviews, 2015).

The study

• Authors: V. Panou, M. Vyberg, U.M. Weinreich, C. Meristoudis, U.G. Falkmer, O.D. Røe
• Journal: Cancer Treatment Reviews
• Published: 2015;41(6):486-95
• Type of article: Review
• Cited by: 69 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Malignant pleural mesothelioma (MPM) is an asbestos-related cancer with a median survival of 12months. The MPM incidence is 1-6/100,000 and is increasing as a result of historic asbestos exposure in industrialized countries and continued use of asbestos in developing countries. Lack of accurate biomarkers makes diagnosis, prognostication and treatment prediction of MPM challenging. The aim of this review is to identify the front line of MPM biomarkers with current or potential clinical impact. Literature search using the PubMed and PLoS One databases, the related-articles function of PubMed and the reference lists of associated publications until April 26th 2015 revealed a plethora of candidate biomarkers. The current gold standard of MPM diagnosis is a combination of two positive and two negative immunohistochemical markers in the epithelioid and biphasic type, but sarcomatous type do not have specific markers, making diagnosis more difficult. Mesothelin in serum and pleural fluid may serve as adjuvant diagnostic with high specificity but low sensitivity. Circulating proteomic and microRNA signatures, fibulin-3, tumor cell gene-ratio test, transcriptomic, lncRNA, glycopeptides, pleural fluid FISH assay, hyaluronate/N-ERC mesothelin and deformability cytometry may be important future markers. Putative predictive markers for pemetrexed-platinum are tumor TS and TYMS, for vinorelbine the ERCC1, beta-tubuline class III and BRCA1. Mutations of the BAP1 gene are potential markers of MPM susceptibility. In conclusion, the current status of MPM biomarkers is not satisfactory but encouraging as more sensitive and specific non-invasive markers are emerging. However, prospective validation is needed before clinical application.

Copyright © 2015 Elsevier Ltd. All rights reserved.

In plain English

This article was a review, not a new study. The authors searched PubMed and PLoS One, and the reference lists of related papers, for English-language articles published up to April 26th 2015 on biomarkers of malignant pleural mesothelioma, an asbestos-related cancer. They described tests for diagnosis, outlook, chemotherapy response and inherited susceptibility. They reported that diagnosis relies on tissue staining with at least two markers expected to be positive and two expected to be negative. They said the sarcomatous type is the hardest to diagnose because it lacks specific markers. Among blood and pleural fluid tests, they discussed soluble mesothelin. They cited one earlier paper reporting 83% sensitivity and 95% specificity, but noted that later analyses found it raised in only 50% of mesothelioma cases. They called fibulin-3 currently unreliable because studies disagreed. They cited reports of inherited BAP1 gene mutations in families with extraordinarily high mesothelioma rates. The authors concluded that promising biomarkers are emerging but that larger studies and prospective validation are needed before clinical use.

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: narrative literature review
• Who was studied: Published literature on malignant pleural mesothelioma biomarkers in the PubMed and PLoS One databases and in reference lists of related publications. Only English-language articles were included, published up to April 26th 2015.
• Exposure: Not studied. The review concerns biomarkers of malignant pleural mesothelioma, not asbestos exposure or fiber types.
• Main results:
  • International Mesothelioma Interest Group recommendations, as reported by the review, require a staining panel of at least two positive and two negative markers to diagnose mesothelioma.
  • Sarcomatous malignant pleural mesothelioma is the most difficult type to diagnose because it lacks specific markers.
  • For soluble mesothelin related protein (SMRP), the review cited an earlier paper by Robinson et al. reporting 83% sensitivity and 95% specificity. It then noted that in subsequent analyses only 50% of mesothelioma cases had elevated SMRP, and SMRP was not elevated in sarcomatous mesothelioma.
  • In a study cited by the review, pleural fluid mesothelin measurement had a sensitivity of 71% versus 35% for cytological examination, and a specificity of 89% versus 100%.
  • The authors judged fibulin-3 currently unreliable because the studies they reviewed disagreed.
  • Germline BAP-1 mutations were described in families with extraordinarily high incidence of mesothelioma and in 25% of sporadic mesothelioma, according to studies cited by the review.
  • None of the candidate markers for predicting chemotherapy response had been validated in independent and prospective cohorts.
• The authors' conclusion: The authors concluded that promising biomarkers are emerging, but further research with larger studies and prospective validation is needed before clinical application.

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: Biomarker, Pleural Mesothelioma, Median Survival, Asbestos Exposure, Epithelioid, Biphasic Mesothelioma, Mesothelin, Fibulin-3.

Related studies

• Expression of thrombomodulin, calretinin, cytokeratin 5/6, D2-40 and WT-1 in a series of primary carcinomas of the lung: an immunohistochemical study in comparison with epithelioid pleural mesothelioma — C.E. Comin, L. Novelli, et al. (2014)
• Hypoxia affects in vitro growth of newly established cell lines from patients with malignant pleural mesothelioma — H. Goudarzi, Y. Hida, et al. (2013)
• Expression of podoplanin and calretinin in meningioma: an immunohistochemical study — M. Shintaku, T. Honda, et al. (2010)
• Expression of Wilms' tumor gene (WT1) is associated with survival in malignant pleural mesothelioma — S. Cedrés, M.A. Montero, et al. (2014)
• GATA3 is a useful immunohistochemical marker for distinguishing sarcomatoid malignant mesothelioma from lung sarcomatoid carcinoma and organizing pleuritis — Z.H. Piao, X.C. Zhou, et al. (2021)
• Diagnostic mesothelioma biomarkers in effusion cytology — A. Eccher, I. Girolami, et al. (2021)

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