Osteopontin reveals the early stages of pleural mesothelioma
October 12, 2005 Medical Research News
Researchers at New York University School of Medicine and Wayne State University have found a molecule that reveals the early stages of pleural mesothelioma, a chest cancer caused by asbestos. The finding opens the way to a blood test for the disease, according to a new study published in the Oct. 13 issue of The New England Journal of Medicine.
An estimated 7.5 million workers in the United States have been exposed to asbestos and, according to government statistics, it remains a hazard to some 1.3 million workers in construction and building maintenance.
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 developing cancer due to asbestos exposure, says Harvey Pass, M.D., Chief of the Division of Thoracic Surgery and Thoracic Oncology in the Department of Cardiothoracic Surgery and Professor of Surgery at NYU School of Medicine, and the lead author of the study.
"The levels of a protein called osteopontin rise dramatically in the early stage of this disease," says Dr. Pass. So, he says, "a rise in the level of this biomarker in workers with past asbestos exposure may indicate to physicians that these people need to be followed even more closely for the development of cancer."
Pleural mesothelioma, a cancer that invades the lining of the chest cavity and the lining of the lungs, usually develops in people who have been exposed to asbestos, such as foundry workers, pipe fitters, shipbuilders, miners, electricians, factory workers, firefighters, as well as construction workers who have used asbestos-containing materials. It often takes decades to develop.
"There are hotspots across the world where this type of cancer is clustered," says Dr. Pass. Such clusters are in the Wittenoom district of Perth, in Western Australia, which has one of the highest incidences of mesothelioma, he says. Other hotspots include Libby, Montana, regions in Quebec, Canada, in France and in Turkey
In the new study, Dr. Pass and colleagues found that blood levels of osteopontin were significantly higher in patients who had pleural mesothelioma compared to individuals who were exposed to asbestos and are at risk for developing the cancer.
The study involved 190 patients. Sixty-nine had asbestos-related nonmalignant disease, such as inflammation which leads to scarring in the lung and plaques on the lining surrounding the lungs; 45 were current or former smokers, who had no previous exposure to asbestos; and 76 patients suffered from pleural mesothelioma and were undergoing surgery.
Those individuals exposed to asbestos for less than 10 years showed the lowest levels of osteopontin. Those levels doubled in people with more than 10 years of exposure. The osteopontin levels rose as changes on their lungs, such as scarring, which were revealed on X rays, became more pronounced. In the patients with documented pleural mesothelioma, blood levels of osteopontin jumped--rising six-fold, even in the earliest stage (stage I) of the disease.
Further research needs to be done to determine the exact levels of the blood that would be used in screening tests for pleural mesothelioma, he says, and validation tests are in the planning stages. "What is crucial," Dr. Pass says, "is that the marker is very encouraging specifically in asbestos-related early-stage disease."
The outlook for pleural mesothelioma patients who are diagnosed late is often grim: they may live only 9 to 12 months. Sadly, fewer than 5 percent of mesothelioma cases are detected early. "There are therapies that will help patients live longer-I would really like to see more patients found early," says Dr. Pass, who also runs outreach programs to find people at risk. "Early detection may find patients before they suffer the ravages of the disease including shortness of breath and pain. 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 with novel therapies for pleural mesothelioma since 1989, and has also sought to use molecular biology tools to find an early detection method, as well as to guide appropriate therapy, for the disease. The discovery of osteopontin in mesothelioma resulted from the analysis of thousands of genes using gene expression arrays.
This study was a collaboration between scientists and clinicians at Wayne State University, the John A. Dingell Veterans Hospital in Detroit, the Cardinal Bernardin Cancer Center, Loyola University, in Maywood, Illinois and the Van Andel Research Institute in Grand Rapids, Michigan. The research was supported in part by a Department of Veterans Affairs Merit Review Award and by patients' donations.
Dr. Pass recently joined NYU School of Medicine. His previous positions
include Chief, Thoracic Oncology at the Karmanos Cancer Institute, Detroit,
which is affiliated with Wayne State University, and Senior Investigator
and Head of the Thoracic Oncology Section of the National Cancer Institute
in Bethesda, Maryland.