Differential diagnosis of malignant pleural mesothelioma on cytology: a gene expression panel versus BAP1 and p16 tests.

Journal of Molecular Diagnostics 2020 February 6 [Link]

Bruno R, Alì G, Poma AM, Proietti A, Libener R, Mariani N, Niccoli C, Chella A, Ribechini A, Grosso F, Fontanini G


Pleural effusions are among the first clinical manifestations of malignant pleural mesothelioma (MPM) and often constitute the only available material for diagnosis. Although an MPM diagnosis can be reliable on cytology, the reported sensitivity is low (30% – 75%). Particularly, it can be hard to discriminate epithelioid MPM, the most common histotype, from reactive mesothelial hyperplasia (MH). Currently, BAP1 and p16, evaluated by immunohistochemistry and fluorescent in situ hybridization respectively, are the most valuable markers to discriminate MPM and MH. Both markers have a high specificity, but their sensitivity is not always satisfying even when used together. We have recently developed a 117 gene expression panel, based on Nanostring technology, able to differentiate epithelioid MPM from MH pleural tissues better than BAP1 and p16. Herein, we evaluated the efficacy of the same panel on an independent retrospective cohort of 23 MPM and 11 MH pleural effusions (cell-blocks, smears). The overall sensitivity and specificity of the panel were equal to 0.9565 and 1 respectively. Moreover, the panel performance was compared with BAP1 and p16 on 25 cell-blocks. Sensitivity of gene panel, BAP1 alone, p16 alone, BAP1 plus p16, were 1, 0.5882, 0.4706 and 0.7647, respectively. Specificity was always 1. Although further validation is needed, this gene panel could really facilitate patients’ management allowing a definitive MPM diagnosis directly on pleural effusions.