Fibulin-3 Represents a Sensitive and Specific Marker for the Diagnosis of Mesothelioma, Offering a Potential Tool for Early Diagnosis, Monitoring

Newswise NEW YORK, October 11, 2012 Researchers at NYU School of Medicine have discovered the protein product of a little-known gene may one day prove useful in identifying and monitoring the development of mesothelioma in early stages, when aggressive treatment can have an impact on the progression of disease and patient prognosis.

This gene produces a protein, fibulin-3, that is present in levels four to five times higher in the plasma of patients with mesothelioma compared to levels in asbestos-exposed patients or patients with several other conditions that cause tumors in the chest, said lead investigator Harvey I. Pass, MD, the Stephen E. Banner Professor of Thoracic Oncology, vice chair of research for the Department of Cardiothoracic Surgery and division chief of General Thoracic Surgery at NYU Langone Medical Center. We didnt know anything about this proteins role in mesothelioma before this study, but it may be an extremely useful tool for monitoring patients under treatment and possibly even diagnosing the development of mesothelioma at early stages. This marker is as exciting as any biomarker in mesothelioma today and warrants further research and validation by the scientific community.

The study appears in the October 11 issue of the New England Journal of Medicine.

Malignant mesothelioma is a rare but aggressive thoracic cancer that can develop several decades after exposure to asbestos. Diagnosis is often delayed until patients begin to show symptoms, including shortness of breath, cough, chest pain and, in advanced stages, weight loss and night sweats.

Often, patients with mesothelioma seek treatment when the shortness of breath becomes a noticeable problem. At that point, an x-ray typically reveals fluid in the chest, but many doctors fail to inquire about asbestos exposure upon receiving this report. Rather, doctors initially associate fluid in the chest with pneumonia or other inflammatory conditions, further delaying diagnosis, Dr. Pass explained.

Despite advances in chemotherapy, radiation therapy, and surgical management for malignant mesothelioma, the median survival for patients diagnosed with mesothelioma remains 12 months.

There is a great need for something some marker or test that will heighten the alarm that a patient presenting with new onset chest fluid could have mesothelioma, Dr. Pass said. Our findings indicate that a simple blood test may lead physicians to ask questions about asbestos exposure and consider whether the medical history and symptoms are compatible with mesothelioma.

Dr. Pass and his team are dedicated to finding diagnostic biomarkers genes, proteins or other molecules that are not only different in people with mesothelioma compared with cancerfree individuals who have been exposed to asbestos, but also different when compared to individuals with a variety of conditions that could cause fluid in the chest other than mesothelioma.

Fibulin-3 is a protein that floats around outside cells, coating the cells and free floating in blood plasma and extracellular fluid. For the current study, the research team compared levels of fibulin-3 in two separate cohorts of patients who were exposed to asbestos through their jobs: a group of iron workers and other asbestos-exposed individuals in Detroit, and a group of insulators in New York. Both cohorts included individuals who had been exposed to asbestos but did not develop mesothelioma, as well as individuals with a confirmed mesothelioma diagnosis. The researchers found that fibulin-3 expression was markedly elevated in the plasma of the patients with mesothelioma compared with the plasma of patients without mesothelioma. But the researchers wondered if maybe the elevated fibulin-3 levels were associated with other conditions, in addition to mesothelioma, that are associated with the development of chest tumors.

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High Levels of Blood-Based Protein Specific to Mesothelioma