A gene‑expression‑based test can outperform bap1 and p16 analyses in the differential diagnosis of pleural mesothelial proliferations

Abstract

The demonstration of tissue invasion by histology is an essential criterion for the differential diagnosis of benign and malignant mesothelial proliferations. When tissue invasion cannot be identified, the use of ancillary tests is sometimes necessary. Among investigated markers, the loss of BRCA1 associated protein 1 (BAP1) protein expression and the homozygous deletion of p16 have shown 100% specificity in separating benign and malignant mesothelial lesions. However, beyond the excellent specificity of these two markers, their low sensitivity limits their clinical utility. In this context, a previous study developed and tested a novel tool for use in the differential diagnosis of malignant pleural mesothelioma (MPM) using the NanoString System and a classification algorithm. In the current study, the performance of gene classifiers were compared using BAP1 and p16 testing. p16 FISH and BAP1 immunohistochemistry were performed on the same series of 34 epithelioid MPM and 20 benign pleural lesions, which were previously analyzed by the system. The diagnostic performance of p16, BAP1 and our classification models were compared using ROC analysis. It was observed that BAP1 loss and p16 deletion were highly specific for MPM, since they were not detected in benign lesions. However, their AUC values were not completely satisfying (BAP1: 0.8235; p16: 0.7647) particularly due to their low sensitivities. As expected, combining BAP1 and p16 tests increased the diagnostic sensitivity, thus improving the AUC (0.8824). In the same series of cases, our MPM tool outperformed BAP1 and p16 tests using the 22 and 40-gene classification models (AUC 22-gene model: 0.9996; AUC 40-gene model: 0.9990). In conclusion, the present gene-expression-based classification exhibited great potential and further validation is required to support these findings in a prospective fashion, in order to provide a solid alternative for pleural proliferation diagnosis.

Reactive mesothelial hyperplasia mimicking mesothelioma in an African green monkey (<i>Chlorocebus aethiops</i>)

“…Mesotheliomas on the other hand are primary tumors of the serosa (Hammar, 1994) and uncommon in animals and humans (Fortman et al, 1993). The occurrence of mesotheliomas in man often had been associated with asbestos (Feder et al, 2018) and -to a lesser extent -other mineral fibers, Simian virus 40 infection, or radiation (Attanoos et al, 2018). Malignant mesotheliomas have been reported in dogs Published by Copernicus Publications on behalf of the Deutsches Primatenzentrum GmbH (DPZ).…”

Validation of a Gene Expression Approach for the Cytological Diagnosis of Epithelioid and Biphasic Pleural Mesothelioma on a Consecutive Series

“…In this context, our group previously developed a 117-gene expression panel and a related classification model able to discriminate epithelioid PM from MH [21]. This panel has already been tested and successfully compared with BAP1 and p16 on two independent retrospective series: one including malignant (epithelioid PM) and benign pleural tissues, giving a sensitivity of 97% and a specificity of 100% [22], and the other including only pleural effusions (both cell blocks and stained smears) with a sensitivity and specificity both equal to 100% [23]. We have already demonstrated that among the 117 genes included in the panel, there are some histotype-specific markers whose expression can help discriminate between biphasic and epithelioid PM [24].…”

Validation of a Gene-Expression Approach for the Cytological Diagnosis of Epithelioid and Biphasic Pleural Mesothelioma on a Consecutive Series

“…In this context, our group has previously developed a 117-gene expression panel and a related classification model able to discriminate epithelioid PM from MH [21]. This panel has already been tested and successfully compared with BAP1 and p16 on two independent retrospective series: one including malignant (epithelioid PM) and benign pleural tissues, giving a sensitivity of 97% and a specificity of 100% [22], and the other including only pleural effusions (both cell-blocks and stained smears) with a sensitivity and specificity both equal to 100% [23]. We have already demonstrated that among the 117 genes included in the panel there are some histotype specific markers, whose expression can help discriminate between biphasic and epithelioid PM [24].…”