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Asbestos-related cancer Screening tool for at risk individuals in sight?
VIENNA – A new serum marker seems promising in the early detection of malignant pleural mesothelioma, a cancer form related to asbestos exposure, explains Kevin Hollevoet, Bio Eng, in his presentation at the 19th Annual Congress of the European Respiratory Society. Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related tumor affecting the membrane that surrounds the lungs. It carries a dismal prognosis: the median survival rate is less than one year. The long latency period between asbestos exposure and tumor presentation, and the continued use of asbestos in developing countries, mean that mesothelioma will remain a worldwide health issue for decades to come. Methods of improving the prognosis are desperately needed. Early-stage diagnosis of the disease seems a potential key to achieving significant progress in MPM management and ultimately to improving survival for those affected. However, diagnosis is difficult, and clinical detection is often delayed by non-specific presenting symptoms, such as shortness of breath or chest-wall pain. Recently, different serum biomarkers have emerged that have the potential to aid in the diagnosis of malignant pleural mesothelioma and in the monitoring of the disease. Two such markers, soluble mesothelin (SM) and megakaryocyte potentiating factor (MPF), both measured in serum with ELISA kits, seem to be the most promising.
Both markers originate from the mesothelin gene product: a precursor protein cleaved into a membrane-bound 40-kDa antigen, mesothelin, and a soluble 31-kDa fraction, MPF. Subsequent cleavage of membrane-bound mesothelin sheds this fraction into the bloodstream as SM. While SM is currently considered the reference serum biomarker of MPM, MPF is hypothesized to have a superior sensitivity due to its favorable release mechanisms in the bloodstream. The first attempt to validate MPF as a biomarker for malignant mesothelioma and to establish its sensitivity as compared to the current gold standard, mesothelin, a study from the Department of Respiratory Medicine, Ghent University Hospital, Belgium, involved 408 individuals. They were recruited in six cohorts: healthy controls (n = 77), healthy asbestos-exposed individuals (n = 85), and patients with benign asbestos-related disease (n = 102), benign respiratory disease (n = 46), lung cancer (n = 53), and MPM (n = 45). Both SM (nmol/L) and MPF levels (ng/mL) differed significantly between MPM patients and individuals in the other cohorts, and the two biomarkers revealed an equivalent diagnostic performance. However, their clinical use is limited to high-specificity settings, and in a diagnostic setting at 95% specificity, including all study participants, the sensitivity of MPF (78%) was superior to that of SM (64%). In addition, by using the 95% specificity cut-off levels, the researchers found that 6 of the 16 MPM patients who were SMnegative were picked up by MPF. In contrast, none of the MPF-negative MPM patients showed elevated SM levels. The use of SM did not add information concerning the presence of MPM, compared to the use of MPF alone, and combining both markers did not improve diagnostic performance. “We have validated MPF in the largest cohort study so far as a MPM biomarker with an overall performance equivalent to SM. However, due to its higher sensitivity in a diagnostic setting, we believe that MPF has the potential to become the marker of choice in MPM management, provided these findings are confirmed in larger series of MPM patients”, explains principal investigator Prof. Jan van Meerbeeck, MD, PhD. “Developing a tool that allows for early detection of this deadly cancer in atrisk populations represents great hope for people known to have been exposed to asbestos.” The ERS is an organization of and for physicians, health professionals, and scientists that advances lung health through programs of education, research, advocacy and practice support that foster excellence in the field of respiratory medicine. For more information, see www.ersnet.org. Abstract Number: 1651 Title: Validation of soluble mesothelin: Design and preliminary results of a Belgian multicentric observational study Author contact: Kevin.hollevoet@ugent.be