{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T00:59:37Z","timestamp":1792803577386,"version":"4.5.0"},"reference-count":29,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Innovation Pool Grant from the University of Zurich","id":[{"id":"https:\/\/ror.org\/02crff812","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Polianthes Foundation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>CDKN2A deletion is a common alteration in pleural mesothelioma (PM) and frequently associated with co-deletion of MTAP. Since the standard detection method for CDKN2A deletion and FISH analysis is relatively expensive, we here investigated the suitability of inexpensive p16 and MTAP IHC by comparing concordance between IHC and OncoScan CNV arrays on samples from 52 PM patients. Concordance was determined using Cohen\u2019s kappa statistics. Loss of CDKN2A was associated with co-deletion of MTAP in 71% of cases. CDKN2A-MTAP copy-number normal cases were also IHC positive in 93% of cases for p16 and 100% for MTAP, while homozygous deletion of CDKN2A-MTAP was always associated with negative IHC for both proteins. In cases with heterozygous CDKN2A-MTAP loss, IHC expression of p16 and MTAP was negative in 100% and 71%, respectively. MTAP and p16 IHC showed high sensitivity (MTAP 86.5%, p16 100%) and specificity (MTAP 100%, p16 93.3%) for the detection of any gene loss. Loss of MTAP expression occurred exclusively in conjunction with loss of p16 labeling. Both p16 and MTAP IHC showed high concordance with Oncoscan CNV arrays (kappa = 0.952, p &lt; 0.0001, and kappa = 0.787, p &lt; 0.0001 respectively). We recommend combined MTAP and p16 immunohistochemistry to confirm the diagnosis of PM.<\/jats:p>","DOI":"10.3390\/cancers15204978","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T10:04:39Z","timestamp":1697191479000},"page":"4978","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Deletions of CDKN2A and MTAP Detected by Copy-Number Variation Array Are Associated with Loss of p16 and MTAP Protein in Pleural Mesothelioma"],"prefix":"10.3390","volume":"15","author":[{"given":"Bart","family":"Vrugt","sequence":"first","affiliation":[{"name":"Institute of Pathology and Molecular Pathology, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7444-9829","authenticated-orcid":false,"given":"Michaela B.","family":"Kirschner","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5546-3120","authenticated-orcid":false,"given":"Mayura","family":"Meerang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"Oehl","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Molecular Pathology, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1751-5866","authenticated-orcid":false,"given":"Ulrich","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Molecular Pathology, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Soltermann","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Molecular Pathology, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7986-2839","authenticated-orcid":false,"given":"Holger","family":"Moch","sequence":"additional","affiliation":[{"name":"Institute of Pathology and Molecular Pathology, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5900-9040","authenticated-orcid":false,"given":"Isabelle","family":"Opitz","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery, University Hospital Zurich, 8091 Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1017-3744","authenticated-orcid":false,"given":"Peter J.","family":"Wild","sequence":"additional","affiliation":[{"name":"Dr. Senckenberg Institute of Pathology (SIP), University Hospital Frankfurt, Goethe University, 60590 Frankfurt am Main, Germany"},{"name":"Wildlab, University Hospital Frankfurt MVZ GmbH, 60596 Frankfurt am Main, Germany"},{"name":"Frankfurt Institute for Advanced Studies (FIAS), 60438 Frankfurt am Main, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1136\/oem.51.12.804","article-title":"Malignant mesothelioma: Attributable risk of asbestos exposure","volume":"51","author":"Spirtas","year":"1994","journal-title":"Occup. 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