Heterogeneity in Malignant Pleural Mesothelioma

Our plain-English summary of Heterogeneity in Malignant Pleural Mesothelioma, by K. Oehl, B. Vrugt, I. Opitz, et al (International Journal of Molecular Sciences, 2018).

The study

• Authors: K. Oehl, B. Vrugt, I. Opitz, M. Meerang
• Journal: International Journal of Molecular Sciences
• Published: 2018;19(6)
• Type of article: Review
• Cited by: 46 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Despite advances in malignant pleural mesothelioma therapy, life expectancy of affected patients remains short. The limited efficiency of treatment options is mainly caused by inter- and intra-tumor heterogeneity of mesotheliomas. This diversity can be observed at the morphological and molecular levels. Molecular analyses reveal a high heterogeneity (i) between patients; (ii) within different areas of a given tumor in terms of different clonal compositions; and (iii) during treatment over time. The aim of the present review is to highlight this diversity and its therapeutic implications.

In plain English

This article is a review, not an original study. The authors summarized published research on how malignant pleural mesothelioma (MPM) varies between patients, within one tumor, and over time during treatment. Gene-sequencing studies included one of 22 tumors that found 490 somatic protein-altering mutations, 477 of them in only one patient each. The authors reported no common mutation 'hotspots' in the genes tested. Cited trials of drugs blocking the protein EGFR showed no benefit. A cited study sampling six patients' tumors at three locations each found clearly distinct mutation patterns. Another cited study of 64 patients found PD-L1 protein staining differed between the main tumor and spread sites in up to 31% of cases. The authors stated that no study had directly assessed MPM change over time and its effect on treatment outcomes, though they described studies finding changes in tumor subtype and protein levels after chemotherapy. Their own preliminary, unpublished data suggested some tumors changed genetically during chemotherapy. The review did not study asbestos exposure. The authors concluded that more studies are needed and that multi-region tumor sampling is required.

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 review
• Who was studied: No study population of its own. The review summarized published studies on malignant pleural mesothelioma tumors, patients, cell lines and animal models.
• Exposure: Not studied. The review mentions asbestos fibers only as the main cause of MPM and does not name fiber types or doses.
• Main results:
  • In a cited exome-sequencing study by Guo et al. of 22 MPM tumors, 490 somatic protein-altering mutations were found. Of these, 477 were private, meaning each was found in only one patient.
  • Across the sequencing studies reviewed, the authors reported no commonly mutated positions or hotspot regions in the genes tested.
  • According to the review, clinical trials of EGFR inhibitors in MPM patients (erlotinib, gefitinib, vandetanib, cetuximab) did not show benefit.
  • A cited study by Kiyotani and colleagues sampled tumors from six MPM patients at three locations each and found clearly distinct mutation patterns between locations.
  • A cited study of 64 MPM patients found that PD-L1 staining differed between the primary tumor and metastatic sites in up to 31% of cases, depending on the reviewer.
  • The authors stated that no study had directly assessed how MPM changes over time and what this means for treatment outcomes.
  • The review described published studies showing changes in MPM after chemotherapy. These included changes in histologic subtype and, in the authors' previous study of matched pre- and post-chemotherapy tissues, reduced expression of PTEN, p-mTOR and p-S6.
  • The authors' own preliminary, unpublished data (manuscript in preparation) suggested that the genetic basis of some MPM tumors changed during chemotherapy.
  • All studies of possible MPM cancer stem cells had isolated them from cell lines.
• The authors' conclusion: The authors concluded that more studies are needed on the different levels of variation within MPM tumors at different time points during treatment. They also concluded that sampling several regions of a tumor is required to identify dominant clones and possibly therapy-resistant subclones.
• Limitations the authors state:
  • The authors stated that knowledge of variation within MPM tumors is still limited and that few publications have addressed it.
  • The authors noted that evidence on cancer stem cells comes from cell lines and that evidence from patient tumor samples is still needed.

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, Life Expectancy, Mesothelioma.

Related studies

• Genetic alterations of malignant pleural mesothelioma: association with tumor heterogeneity and overall survival — L. Quetel, C. Meiller, et al. (2020)
• Multi-site tumor sampling highlights molecular intra-tumor heterogeneity in malignant pleural mesothelioma — C. Meiller, F. Montagne, et al. (2021)
• Autotaxin signaling governs phenotypic heterogeneity in visceral and parietal mesothelia — E.L. Shelton, C.L. Galindo, et al. (2013)
• Non-Coding Transcript Heterogeneity in Mesothelioma: Insights from Asbestos-Exposed Mice — E. Felley-Bosco, H. Rehrauer (2018)
• Special Issue on Mechanisms of Mesothelioma Heterogeneity: Highlights and Open Questions — E. Felley-Bosco (2018)
• Mesothelioma cell heterogeneity identified by single cell RNA sequencing — L. Wu, Z. Wang, et al. (2025)

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