Pathogenesis of malignant mesothelioma.
Malignant mesothelioma (MM) is a very aggressive tumor that is caused by environmental, biologic, and genetic factors. Among these factors, asbestos plays a major role. The link between asbestos and MM has been firmly established through numerous epidemiologic studies conducted during the past 40 years. However, the causal role of chrysotile asbestos compared with crocidolite asbestos in MM, the method of correctly establishing asbestos exposure, the amount of asbestos necessary to cause MM, and the mechanisms of asbestos tumorigenicity are still being debated. Along with asbestos, Simian virus 40 (SV40), a DNA monkey virus, has recently been implicated in the etiology of MM. Simian virus 40 large T antigen (Tag) and small t antigen (tag) are largely responsible for the carcinogenicity of the virus, and it is possible that SV40 and asbestos are cocarcinogens. Finally, a genetic factor identified in 3 villages in Cappadocia, Turkey, where 50% of individuals die of MM, appears to be the cause of a high incidence of the disease. In these villages, genetic predisposition for MM works together with erionite, a nonasbestos fiber found in the stones used in construction of houses. The diagnosis of MM is made histologically and confirmed through electron microscopy and immunohistochemistry. Currently available therapies for MM prolong survival by a few months at most. An SV40 vaccine is being developed for human use and it is hoped that it may reduce the incidence of MM in asbestos workers.
Carbone
Michele
M
Cancer Immunology Program, Department of Pathology, Cardinal Bernardin Cancer Center, Loyola University Chicago, Maywood, IL 60153, USA. mcarbon@orion.it.luc.edu
Rdzanek
Monica A
MA
D000818:Animals; D001194:Asbestos / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity; D006801:Humans; D008654:Mesothelioma / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D009784:Occupational Diseases / Q000209:etiology / Q000503:physiopathology; D016273:Occupational Exposure / Q000009:adverse effects; D010997:Pleural Neoplasms / Q000209:etiology / Q000503:physiopathology* / Q000628:therapy; D012737:Sex Factors; D013539:Simian virus 40; D014412:Tumor Virus Infections / Q000209:etiology / Q000628:therapy; D014765:Viral Vaccines / Q000008:administration & dosage
D002273:Carcinogens; D014765:Viral Vaccines; D001194:Asbestos