Diagnosing Pleural Mesothelioma with Lung Fluid: The Battle of the Biomarkers

Biologist Holding FlasksA biomarker called soluble mesothelin related peptide (SMRP) may be a more reliable way to diagnose malignant pleural mesothelioma from lung fluid than the protein fibulin-3.

That is the finding of Italian researchers who tested the diagnostic performance of the two markers in 120 patients, including 33 mesothelioma patients, in an effort to resolve what they call “conflicting data” on the two methods.

SMRP and Fibulin-3

SMRPs are produced by the breakdown of proteins in the membranes surrounding the lungs, heart, and abdomen. The amount of SMRP in the blood is thought to be related to the extent of malignant mesothelioma in the body.

Fibulin-3 (FBLN) is an extracellular matrix protein expressed in the membranes of blood vessels. A 2012 study published in the New England Journal of Medicine suggested that measuring the amount of FBLN3 in the plasma of people with pleural mesothelioma could help distinguish them from people with pleural effusions not due to mesothelioma.

Subsequent studies, however, have found FBLN3 potentially more useful for predicting how well a patient is likely to respond to mesothelioma treatment, than as a diagnostic tool.

Comparing Mesothelioma Biomarkers

In their new study, cancer researchers with Italy’s regional health service in La Spezia compared the diagnostic accuracy of FBLN3 and SMRP in patients with excess lung fluid called pleural effusions. The buildup of fluid around the lungs can be caused by a malignancy like pleural mesothelioma or by a non-malignant condition.

To assess how the biomarkers performed in both types of conditions, the research team included 33 patients with malignant pleural mesothelioma, 64 patients with benign tumors on their pleural membranes and 23 patients with other types of cancer that had metastasized to the pleura.

“Levels of FBLN3 were similar in pleural effusions from malignant pleural mesothelioma and pleural effusions from other pathologies,” writes clinical pathology researcher Enrico Battolla. “[This is] in contrast to SMRP levels, which were significantly higher in pleural effusions from malignant pleural mesothelioma.”

SMRP Once Again Best Biomarker for Mesothelioma

The team concluded that FBLN3 was “not useful” as a diagnostic biomarker in the pleural effusions of people with malignant pleural mesothelioma since it was unable to discriminate mesothelioma from other causes of pleural effusions.

SMRP, on the other hand, was determined to be useful, a finding consistent with previous studies. Even with biomarkers for guidance, diagnosing mesothelioma remains a complex process, involving imaging studies, a thorough physical exam, and a careful history of potential asbestos exposure.

FBLN3 is still considered to be a useful mesothelioma prognostic marker. Other biological markers for prognosis include the ratio of neutrophils to lymphocytes in the blood (a measure of how well the immune system is functioning), c-MET expression (associated with blood vessel formation for the tumor), and ki-67 ratios (associated with cancer cell proliferation).


Battolla, E, et al, “Comparison of the Diagnostic Performance of Fibulin-3 and Mesothelin in Patients with Pleural Effusions from Malignant Mesothelioma”, March 2017, Anticancer Research, pp. 1387-131. 

Creaney, J, et al, “Comparison of mesothelin and fibulin-3 in pleural fluid and serum as markers in malignant mesothelioma”, Mary 26, 2015, Current Opinions in Pulmonary Medicine, Epub ahead of print

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