Researchers at New York University School of Medicine and Wayne StateUniversity have found a molecule that reveals the early stages ofpleural mesothelioma, a chest cancer caused by asbestos. The findingopens the way to a blood test for the disease, according to a new studypublished in the Oct. 13 issue of The New England Journal of Medicine.
An estimated 7.5 million workers in the United States have been exposedto asbestos and, according to government statistics, it remains ahazard to some 1.3 million workers in construction and buildingmaintenance.
There has been no way to reliably screen for this type of cancer,particularly in its early stages when treatment may be more successful.The blood test could help to monitor people at risk of developingcancer due to asbestos exposure, says Harvey Pass, M.D., Chief of theDivision of Thoracic Surgery and Thoracic Oncology in the Department ofCardiothoracic Surgery and Professor of Surgery at NYU School ofMedicine, and the lead author of the study.
"The levels of a protein called osteopontin rise dramatically in theearly stage of this disease," says Dr. Pass. So, he says, "a rise inthe level of this biomarker in workers with past asbestos exposure mayindicate to physicians that these people need to be followed even moreclosely for the development of cancer."
Pleural mesothelioma, a cancer that invades the lining of the chestcavity and the lining of the lungs, usually develops in people who havebeen exposed to asbestos, such as foundry workers, pipe fitters,shipbuilders, miners, electricians, factory workers, firefighters, aswell as construction workers who have used asbestos-containingmaterials. It often takes decades to develop.
"There are hotspots across the world where this type of cancer isclustered," says Dr. Pass. Such clusters are in the Wittenoom districtof Perth, in Western Australia, which has one of the highest incidencesof mesothelioma, he says. Other hotspots include Libby, Montana,regions in Quebec, Canada, in France and in Turkey.
Blood levels of a protein called osteopontin
In the new study, Dr. Pass and colleagues found that blood levels ofosteopontin were significantly higher in patients who had pleuralmesothelioma compared to individuals who were exposed to asbestos andare at risk for developing the cancer.
The study involved 190 patients. Sixty-nine had asbestos-relatednonmalignant disease, such as inflammation which leads to scarring inthe lung and plaques on the lining surrounding the lungs; 45 werecurrent or former smokers, who had no previous exposure to asbestos;and 76 patients suffered from pleural mesothelioma and were undergoingsurgery.
Those individuals exposed to asbestos for less than 10 years showed thelowest levels of osteopontin. Those levels doubled in people with morethan 10 years of exposure. The osteopontin levels rose as changes ontheir lungs, such as scarring, which were revealed on X rays, becamemore pronounced. In the patients with documented pleural mesothelioma,blood levels of osteopontin jumped--rising six-fold, even in theearliest stage (stage I) of the disease.
Further research needs to be done to determine the exact levels of theblood that would be used in screening tests for pleural mesothelioma,he says, and validation tests are in the planning stages. "What iscrucial," Dr. Pass says, "is that the marker is very encouragingspecifically in asbestos-related early-stage disease."
About pleural mesothelioma and the biomarker
The outlook for pleural mesothelioma patients who are diagnosed late isoften grim: they may live only 9 to 12 months. Sadly, fewer than 5percent of mesothelioma cases are detected early. "There are therapiesthat will help patients live longer--I would really like to see morepatients found early," says Dr. Pass, who also runs outreach programsto find people at risk. "Early detection may find patients before theysuffer the ravages of the disease including shortness of breath andpain. At this point in time, surgery, radiation therapy, chemotherapy,and new targeted therapies may help extend patients' lives."
Dr. Pass has been exploring surgical approaches in combination withnovel therapies for pleural mesothelioma since 1989, and has alsosought to use molecular biology tools to find an early detectionmethod, as well as to guide appropriate therapy, for the disease. Thediscovery of osteopontin in mesothelioma resulted from the analysis ofthousands of genes using gene expression arrays.
This study was a collaboration between scientists and clinicians atWayne State University, the John A. Dingell Veterans Hospital inDetroit, the Cardinal Bernardin Cancer Center, Loyola University, inMaywood, Illinois and the Van Andel Research Institute in Grand Rapids,Michigan. The research was supported in part by a Department ofVeterans Affairs Merit Review Award and by patients' donations.
Dr. Pass recently joined NYU School of Medicine. His previous positionsinclude Chief, Thoracic Oncology at the Karmanos Cancer Institute,Detroit, which is affiliated with Wayne State University, and SeniorInvestigator and Head of the Thoracic Oncology Section of the NationalCancer Institute in Bethesda, Maryland.
Materials provided by New York University Medical Center and School of Medicine. Note: Content may be edited for style and length.
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