Biomarkers used to distinguish mesothelioma from noncancerous tissue
The difficult differential diagnosis between malignant pleural mesothelioma (MPM) and noncancerous pleural tissue with reactive mesothelial proliferations (RMPs) may be aided by four biomarkers, identified by scientists from Copenhagen University Hospital (Copenhagen, Denmark).
Enabling more accurate diagnoses when dealing with pleural biopsy samples taken from patients with clinical suspicion of MPM may facilitate improved patient outcomes, as this is a frequent differential diagnostic problem.
As there are currently no generally accepted diagnostic biomarkers for distinguishing MPM from noncancerous abnormalities, such as reactive mesothelial hyperplasia or fibrous pleurisy (organizing pleuritis), differentiating the two conditions can be difficult.
This leads to patients often presenting with the disease when they are already at an advanced stage, and less than 20% of patients can be successfully treated surgically. MPM is an aggressive cancer, which is linked to long-term asbestos exposure, and originates from the mesothelial cells that line the membrane surrounding each lung, known as the pleura.
“Our goal was to identify microRNAs (miRNAs) that can aid in the differential diagnosis of MPM from RMPs,” explained lead investigator Eric Santoni-Rugiu, of the Laboratory of Molecular Pathology at the Department of Pathology of Rigshospitalet, Copenhagen University Hospital. miRNAs, small, noncoding RNA strands composed of approximately 22 nucleotides, have been shown to be potential diagnostic, prognostic and predictive markers in other cancers.
In the study, published in the Journal of Molecular Diagnostics, 742 miRNAs were screened and, as a result, the researchers identified miR-126, miR-143, miR-145 and miR-652 as the best candidates to diagnose MPM. Results from these four miRNAs were then used to classify tissue samples from patients with known outcomes as MPM or noncancerous, with an accuracy of 0.94, sensitivity of 0.95 and specificity of 0.93.
An association between miRNA levels and patient survival could also be made. Santoni-Rugiu described how “The International Mesothelioma Interest Group (IMIG) recommends that a diagnostic marker of MPM have sensitivity/specificity of >0.80, and these criteria are fulfilled by our miRNA classifier.”
The scientists suggest that diagnostic accuracy can be further improved by adding immunohistochemical testing of miRNA targets in biopsy tissue to their miRNA assay. This combined assay could enable analysis of samples with low tumor cell count. The current study, however, suggests that miRNAs may provide new opportunities for improving the accuracy of the differential diagnosis between MPM and noncancerous pleural conditions.
Source: Andersen M, Grauslund M, Ravn J, Sørensen JB, Andersen CB, Santoni-Rugiu E. Diagnostic potential of miR-126, miR-143, miR-145, and miR-652 in malignant pleural mesothelioma. J. Mol. Diagn. 16(4), 418–430 (2014).
