{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:47:30Z","timestamp":1792450050959,"version":"4.5.0"},"reference-count":46,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T00:00:00Z","timestamp":1630627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2022,2]]},"abstract":"<jats:p>Cytology effusions are often the only material available for diagnosing malignant pleural mesothelioma (MPM). However, the cytomorphological features alone are not always diagnostic, and cytology samples preclude an assessment for pleural tissue invasion. Accordingly, immunohistochemical, soluble, and molecular biomarkers have been developed. The aim of this study is to provide quantitative evidence regarding the diagnostic performance of novel biomarkers. To that end, a systematic literature review was performed of articles dealing with a loss of BRCA1\u2010associated protein 1 (BAP1), methylthioadenosine (MTAP), 5\u2010hydroxymethylcitosine (5\u2010hmC), glucose transporter 1 (GLUT1), insulin like\u2010growth factor II messenger RNA\u2013binding protein 3 (IMP3), enhanced zeste homologue 2 (EZH2) staining, cyclin\u2010dependent kinase inhibitor 2A (<jats:italic>CDKN2A<\/jats:italic>) homozygous deletion (HD) testing, soluble mesothelin, and microRNA quantification in cytological samples for the diagnosis of MPM versus reactive atypical mesothelial cells. Sensitivity and specificity were extracted, and a meta\u2010analysis was performed. The quality of the studies was assessed with Quality Assessment of Diagnostic Accuracy Studies 2, and the quality of the evidence was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation approach. Seventy\u2010one studies were included. BAP1 loss showed a sensitivity of 0.65 (confidence interval [CI], 0.59\u20100.71) and a specificity of 0.99 (CI, 0.93\u20101.00). MTAP loss and p16 HD showed 100% specificity with sensitivities of 0.47 (CI, 0.38\u20100.57) and 0.62 (CI, 0.53\u20100.71), respectively. BAP1 loss and <jats:italic>CDKN2A<\/jats:italic> HD combined showed maximal specificity and a sensitivity of 0.83 (CI, 0.78\u20100.89). GLUT1 and IMP3 showed sensitivities of 0.82 (CI, 0.70\u20100.90) and 0.65 (CI, 0.41\u20100.90), respectively, with comparable specificity. Mesothelin showed a sensitivity of 0.73 (CI, 0.68\u20100.77) and a specificity of 0.90 (CI, 0.84\u20100.93). In conclusion, some of the recently emerging biomarkers are close to 1.00 specificity. Their moderate sensitivity on their own, however, can be significantly improved by the use of 2 biomarkers, such as a combination of BAP1 and <jats:italic>CDKN2A<\/jats:italic> with fluorescence in situ hybridization or a combination of BAP1 and MTAP immunohistochemistry.<\/jats:p>","DOI":"10.1002\/cncy.22509","type":"journal-article","created":{"date-parts":[[2021,9,3]],"date-time":"2021-09-03T12:00:42Z","timestamp":1630670442000},"page":"96-109","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Evidence\u2010based diagnostic performance of novel biomarkers for the diagnosis of malignant mesothelioma in effusion cytology"],"prefix":"10.1002","volume":"130","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3537-4929","authenticated-orcid":false,"given":"Ilaria","family":"Girolami","sequence":"first","affiliation":[{"name":"Division of Pathology Central Hospital Bolzano Bolzano Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ersilia","family":"Lucenteforte","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Pisa Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9992-5550","authenticated-orcid":false,"given":"Albino","family":"Eccher","sequence":"additional","affiliation":[{"name":"Department of Pathology and Diagnostics University and Hospital Trust of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Marletta","sequence":"additional","affiliation":[{"name":"Section of Pathology Department of Diagnostics and Public Health University and Hospital Trust of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Brunelli","sequence":"additional","affiliation":[{"name":"Section of Pathology Department of Diagnostics and Public Health University and Hospital Trust of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Graziano","sequence":"additional","affiliation":[{"name":"Pathology Unit Foundation IRCCS Casa Sollievo Della Sofferenza San Giovanni Rotondo Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6429-0620","authenticated-orcid":false,"given":"Pasquale","family":"Pisapia","sequence":"additional","affiliation":[{"name":"Department of Public Health University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Umberto","family":"Malapelle","sequence":"additional","affiliation":[{"name":"Department of Public Health University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1630-5805","authenticated-orcid":false,"given":"Giancarlo","family":"Troncone","sequence":"additional","affiliation":[{"name":"Department of Public Health University of Naples Federico II Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aldo","family":"Scarpa","sequence":"additional","affiliation":[{"name":"Department of Pathology and Diagnostics University and Hospital Trust of Verona Verona Italy"},{"name":"Section of Pathology Department of Diagnostics and Public Health University and Hospital Trust of Verona Verona Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan Ann Arbor 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