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Biomarker Rise Thought to Precede Onset of Mesothelioma

The most up-to-date study out of Germany details the news that a rise in mesothelin (a tumor marker) could point the way to diagnosis of mesothelioma.

Pleural mesothelioma is a rare but venomous cancer related primarily with industrial exposure to asbestos. Researchers with the Institute of Occupational and Social Medicine in Aachen, Germany say their findings imply that levels of the proteins mesothelin and osteopontin, recognized to be elevated in asbestos-exposed workers, may climb sharply within the months prior to the onset of symptoms. As well, a rise is absolutely not necessarily a precursor to disease.

Mesothelin is a protein present in regular mesothelial cells. But because it is overexpressed in several different types of cancer, including mesothelioma, ovarian and pancreatic cancers, is has increasingly been used as a biomarker to indicate the presence of cancer. Osteopontin is a multifunctional protein involved in a number of varied biological processes and associated with tumorgenesis. Even though it is not a specific biomarker for mesothelioma, some scientific studies have supported its use as one indicator in a panel of biomarkers.

The goal of the German study was to determine how much these biomarker levels might change before asbestos-exposed workers developed asbestos-related diseases like mesothelioma or lung cancer. Is there a degree of change which may be �normal� over time and not an indication of the fact that worker should have an intensive clinical workup?

To answer that problem, the research team analyzed 3,329 blood sampled from 2,262 participants. Just under 1,900 of the participants were formerly asbestos-exposed power industry workers, 266 of them were a mixed group with an unidentified history of asbestos exposure, and 102 had no history of contact with asbestos. The concentration of mesothelin and osteopontin of their blood was determined using commercial ELISA test kits.

�While age had a powerful influence on marker levels, there is no association between exposure duration or benign asbestos-related disease and marker levels,� observed the researchers. They then separated out patients who had a minimum of a 10% increase in mesothelin and/or osteopontin levels. The highest (95th percentile) of those patients had an annual increase of 0.402 nmol/l for mesothelin and 334 ng/ml for osteopontin but most still didn't develop mesothelioma. However, two of the folks who did go on to develop mesothelioma and 5 of the folks who got lung cancer had even higher levels than these before they developed symptoms. The mesothelioma patients specifically both had a �steep increase� in mesothelin levels.

The researchers say their findings imply that having fixed cut-off values for selecting who needs a physician�s evaluation and who can continue to be monitored are �insufficient� since some participants had drastically elevated biomarker levels with no disease. Nonetheless, the rapid and dramatic rise within the mesothelin levels of 2 of the mesothelioma sufferers prompted them to conclude the article in this way: �While general conclusions cannot be drawn, we can say that the results of the two patients would be in step with a mesothelin increase between six and 18 months before clinical symptoms developed.�

The study appears in the recent issue of the International Archives of Occupational and Environmental Health.

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