Mesothelioma pathogenesis, facts and expectations

Our plain-English summary of Mesothelioma pathogenesis, facts and expectations, by M.C. Jaurand (Pathologie-biologie, 2005).

The study

• Author: M.C. Jaurand
• Journal: Pathologie-biologie
• Published: 2005;53(1):41-4
• Type of article: Review
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

It is the merit of Dr J.C. Wagner and his co-workers to have triggered the research on mesothelioma, going back to 1960 when they published data demonstrating a relationship between mesothelioma occurrence and exposure to asbestos fibres in the Cape Province, in South Africa. From that time, epidemiological and toxicological investigations were performed in order to better define the occupational and environmental background of this pathology, to identify the fibre parameters accounting for the toxic effects, and to understand their mechanisms of action. Improvements in our knowledge in these areas benefited to health issues, by preventing risks associated with exposure to mineral fibres and by recognising the disease. Due to the actual progresses in the fields of biology and biotechnologies, the research on mesothelioma presently focuses on study of the mechanisms of mesothelial cell transformation, and on development of strategies to kill tumour cells. While mesothelioma benefited to fibre toxicology and allowed to improve the management health related issue, it would be a just return if the present advances in different scientific areas will permit a rapid eradication of the disease.

In plain English

This article was a short narrative review placing findings from the author's laboratory within what was then known about how mesothelioma develops. It recalled Wagner and co-workers' 1960 report of mesothelioma cases in the north west Cape Province, South Africa, where crocidolite asbestos was exploited. It described a 30 to 40 year latency between the start of exposure and diagnosis. Citing earlier experiments, it stated that long, thin fibres were the most tumour-causing and that chrysotile and crocidolite were both carcinogenic in animals. Citing other studies, it reported that about 20% of mesothelioma cases had no evidence of asbestos exposure and that NF2 was mutated in about 30% of mesotheliomas. The author's group had reported more mesotheliomas in asbestos-exposed mice missing one Nf2 gene copy than in normal mice. The group had also detected SV40 DNA sequences in several mesothelioma samples, as well as in broncho-pulmonary carcinoma and benign pleuresia. In France, mesothelioma cases rose between 1997 and 2000 at rates of +4.76% in men and +6.83% in women. The author called for sustained effort to eradicate the disease.

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 (short perspective article) summarizing published research on mesothelioma pathogenesis, including the author's own laboratory's earlier work
• Who was studied: No study population of its own. The review covered human epidemiological findings, human mesothelioma cell lines and tumour samples, and animal experiments (rats, mice) described in earlier publications.
• Exposure: Asbestos fibres: serpentine (chrysotile) and amphiboles (amosite, crocidolite). The review also discussed man-made vitreous fibres and the simian virus SV40 as a possible other factor.
• Main results:
  • The review described Wagner and co-workers' earlier report of mesothelioma cases in the north west of Cape Province, South Africa, where crocidolite asbestos was exploited. Those patients were exposed at work or in the environment.
  • The review stated a latency period of 30 to 40 years between the beginning of exposure and diagnosis.
  • Citing earlier animal work, the review stated that chrysotile and crocidolite were both carcinogenic to the pleura and the lung in animal experiments. It also described a hypothesis that chrysotile, being less stable, reaches the pleura in a modified state.
  • Citing other studies, the review stated that TP53 mutation was infrequent in mesothelioma, while the genes P16CDKN2A and P15CDKN2B were frequently altered.
  • The author's laboratory did not find SV40 expression in its mesothelioma cell lines. It did detect SV40 DNA sequences in several mesothelioma samples, and also in broncho-pulmonary carcinoma and in benign pleuresia. The author concluded that SV40 is not specific to mesothelioma.
  • Citing a French case-control study, the review stated that about 20% of mesothelioma cases had no evidence of asbestos exposure.
  • Citing earlier studies, the review stated that the NF2 tumour suppressor gene was mutated in about 30% of mesotheliomas.
  • The author's group had previously reported a higher frequency of mesotheliomas in asbestos-exposed mice carrying only one copy of the Nf2 gene (hemizygous) than in normal (wild-type) mice. Both copies of the gene were inactivated in the tumours.
  • In a phase I gene therapy trial in mesothelioma described by the review, the treatment was safe and some degree of tumour reduction was observed.
  • In France, the increase in mesothelioma cases between 1997 and 2000 was +4.76% in men and +6.83% in women. The review described these as among the highest rates in men and the highest in women.
• The authors' conclusion: The author concluded that mesothelioma is a public health concern, that a sustained effort is needed to eradicate it, and that basic and applied research on mesothelioma is needed.
• Limitations the authors state:
  • The author noted that the proposal that asbestos carries out some of the genetic steps in multistep carcinogenesis rests on a limited number of data.
  • The author noted that measuring fibre content in lung and pleura gives only a late signature of exposure, because fibres are cleared with time.
  • The author noted that no comparative data were available on SV40 in asbestos-exposed versus unexposed mesothelioma cases.

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelioma, Cape Province, Pathology, Mesothelial Cells.

Related studies

• OV632 as a possible marker for malignant mesothelioma: high expectations; low specificity — A. Abati, P.A. Fetsch (1995)
• Living beyond expectations: a qualitative study into the experience of long-term survivors with pleural mesothelioma and their carers — M. Johnson, P. Allmark, et al. (2022)
• Malignant mesothelioma: facts, myths, and hypotheses — M. Carbone, B.H. Ly, et al. (2012)
• Asbestosis mortality in the USA: facts and predictions — V.C. Antao, G.A. Pinheiro, et al. (2009)
• Facts and fiction: premalignant lesions of lung tissues — S. Klebe, D.W. Henderson (2013)
• Asbestos as a hazard to health. Fact and speculation — W.C. Cooper (1967)

Browse return to medical research.