Current Status of Screening for Malignant Pleural Mesothelioma

https://doi.org/10.1053/j.semtcvs.2009.06.007Get rights and content

Malignant mesothelioma is characterized by its association with asbestos, its long latency period, and the propensity for the diagnosis to be obtained in the later stages of the disease. Because the high-risk cohorts for mesothelioma are fairly well defined by the association with asbestos, and the exposure is usually in the workplace, it is hypothesized that early detection of the disease could (1) find patients at an earlier, more treatable stage and (2) result in prolonged survival over the present median 12 months from the start of therapy. Many studies have used standard chest X-ray to characterize changes associated with asbestos-exposed individuals, but the insensitivity of X-ray in screening patients with mesothelioma has never supported the wide-scale adaptation of such an effort. With the advent of computerized tomography, prospective trials, many of which are chiefly prevalence detection studies, have been performed and stress the importance for proper detailing by carefully qualifying suspicious changes, as well as defining the correct cohort to screen. Most recently, serum biomarkers with the potential to discriminate asbestos-exposed, non-cancer-bearing individuals from those with mesothelioma have been investigated both at single institutions and with multi-institutional-blinded trials. These markers, including soluble mesothelin-related protein, osteopontin, and megakaryocyte potentiating factor, may, in the future, be incorporated into a screening algorithm for high-risk asbestos-exposed individuals to help monitor these cohorts in a noninvasive fashion and guide the use of computerized tomography.

Section snippets

Populations At-Risk of Developing MM

Since Wagner's cohort report of MM cases in South African mine workers in 1960, asbestos has been implicated as the principal etiology of this cancer.4 The asbestos exposure history usually predates diagnosis by 20-50 years and may be brief but intense. Particular occupations at risk for high exposure include miners, factory workers, carpenters, electricians, navy personnel, insulation manufacturers, railroad workers, ship builders, gas mask manufacturers, and workers in the construction

Failure of Asbestos Surveillance Methods

Asbestos-exposed workers have justifiable anxiety about their future and seek reassurance from the medical profession. Since 1973, the USA Occupational Safety and Health Administration has mandated monitoring of individuals with occupations that involve asbestos exposure. Employers must provide comprehensive medical examinations for every employee exposed to airborne concentrations of asbestos fibers. These examinations include a posterior-anterior chest X-ray, a complete history to elicit

Previous Biomarker Studies

Many studies have attempted to define serum biomarkers that predate symptoms in a “high-risk” population as well as distinguish MM from other malignancies. Most of these studies have had very few patients in various stages of disease and have not been prospectively evaluated. A battery of serum biomarkers was evaluated for early detection of malignancy and for distinguishing early stages of MM and bronchogenic carcinoma, but only 4 markers (namely, tissue polypeptide antigen, carcinoembyonic

Soluble Mesothelin-related Protein

Soluble mesothelin-related protein (SMRP) is related to the mesothelin family of molecules. Mesothelin is expressed by normal mesothelial cells46; however, it is highly overexpressed in cancers, such as MM,47, 48 pancreatic,49 or ovarian carcinoma47, 50 and data from our laboratory using serial analysis of gene expression confirm that the mesothelin levels are 49-fold increased over normal peritoneum.51 Differential posttranscriptional and posttranslational processing of the mesothelin gene

Conclusions

Previous large-scale radiologic screening studies with plain chest X-ray and CT scanning have proved ineffective for detecting early stage MM among asbestos-exposed individuals. Future prospects hinge on the identification and validation of effective biomarkers of this disease. At present, however, there are no validated biomarkers which in prospective trials have proved to have sufficient specificity and sensitivity for adaptation to the clinic. SMRP, OPN, and MPF all are promising but none of

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