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

Rossella Bruno; Anello Marcello Poma; Greta Alì; Agnese Proietti; Alessandro Ribechini; Antonio Chella; Gabriella Fontanini

doi:10.3390/cancers15235534

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

Cancers (Basel). 2023 Nov 22;15(23):5534. doi: 10.3390/cancers15235534.

Authors

Rossella Bruno¹, Anello Marcello Poma², Greta Alì², Agnese Proietti¹, Alessandro Ribechini³, Antonio Chella⁴, Gabriella Fontanini²

Affiliations

¹ Unit of Pathological Anatomy, University Hospital of Pisa, Via Roma 67, 56126 Pisa, Italy.
² Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, Via Savi 10, 56126 Pisa, Italy.
³ Endoscopic Section of Pneumology, University Hospital of Pisa, Via Paradisa 2, 56124 Pisa, Italy.
⁴ Unit of Pneumology, University Hospital of Pisa, Via Paradisa 2, 56124 Pisa, Italy.

Abstract

Cytological diagnosis of pleural mesothelioma (PM) is controversial, even using ancillary markers (BAP1, MTAP and CDKN2A). Here, we aimed to prospectively validate a previously developed 117-gene expression panel for the differential cytological diagnosis of epithelioid, biphasic PM and mesothelial hyperplasia. Seventy-seven pleural effusions were classified using the 117-gene expression levels (NanoString system). Sixty-eight cases were also screened for ancillary markers. The performance of both gene panel and ancillary markers was evaluated using ROC metrics. A score using the top consistently deregulated genes between epithelioid and biphasic PM was built to subtype malignant effusions. The panel alone reached a diagnostic accuracy (0.89) comparable to the best marker combination (BAP1 plus MTAP: 0.88). Ancillary tests missed 8 PMs, 7 of which were correctly classified by the panel. The score built by averaging the expression levels of MSLN, CLDN15 and CFB showed an accuracy of 0.80 in subtyping epithelioid and biphasic effusions. The 117-gene panel is effective for PM cytological diagnosis of epithelioid and biphasic PM. This tool can be complementary to ancillary markers, reducing invasive procedures and allowing an earlier diagnosis. Finally, the possibility to subtype PM on effusions strengthens the panel's role in PM diagnosis and management.

Keywords: gene expression; mesothelial hyperplasia; pleural effusions; pleural mesothelioma; subtyping.

Grants and funding

Reagents and consumables were obtained with funds from the University of Pisa (no specific grant number). The nCounter mesothelioma custom-panel was provided by NanoString Technologies Inc.