{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:47:34Z","timestamp":1792450054146,"version":"4.5.0"},"reference-count":45,"publisher":"Archives of Pathology and Laboratory Medicine","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,1]]},"abstract":"<jats:sec>\n                    <jats:title>Context.\u2014<\/jats:title>\n                    <jats:p>Homozygous deletion (HD) of CDKN2A is one of the most frequent genetic abnormalities in pleural mesotheliomas. HD of CDKN2A by fluorescence in situ hybridization (FISH) is a reliable marker of malignancy in mesothelial proliferations; however, evaluation of CDKN2A deletion requires FISH. The 9p21 locus includes both CDKN2A and MTAP (methylthioadenosine phosphorylase); the latter is frequently codeleted with CDKN2A.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective.\u2014<\/jats:title>\n                    <jats:p>To examine the question of whether immunohistochemistry for MTAP and p16, the protein product of CDKN2A, can serve as a surrogate for CDKN2A HD by FISH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design.\u2014<\/jats:title>\n                    <jats:p>A random selection of 125 pleural mesothelioma cases was divided into 3 groups for evaluation of p16 and MTAP expression compared with FISH for CDKN2A deletion: 53 with HD, 39 with heterozygous deletion, and 33 without deletion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results.\u2014<\/jats:title>\n                    <jats:p>By itself, loss of p16 nuclear expression (&amp;lt;1% staining) showed a high sensitivity (96%) but low specificity (43%) for CDKN2A HD by FISH. MTAP cytoplasmic expression loss (\u226430% staining) showed a 97% specificity and 69% sensitivity. The combination of p16 nuclear (&amp;lt;1% staining) and MTAP cytoplasmic (\u226430% staining) loss demonstrated both high specificity (96%) and high sensitivity (86%). Patients with retained p16 expression (\u22651%) had the best prognosis, whereas a p16 (&amp;lt;1%)\/MTAP loss combination was associated with a dismal prognosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions.\u2014<\/jats:title>\n                    <jats:p>MTAP immunohistochemical staining is a valid surrogate marker for CDKN2A HD by FISH; however, to obtain the same accuracy as the FISH assay, a combination of nuclear p16 and cytoplasmic MTAP staining is recommended. These findings correlate with prognosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.5858\/arpa.2021-0331-oa","type":"journal-article","created":{"date-parts":[[2022,6,23]],"date-time":"2022-06-23T17:36:29Z","timestamp":1656005789000},"page":"313-322","source":"Crossref","is-referenced-by-count":25,"title":["A Combination of MTAP and p16 Immunohistochemistry Can Substitute for\n                    <i>CDKN2A<\/i>\n                    Fluorescence In Situ Hybridization in Diagnosis and Prognosis of Pleural Mesotheliomas"],"prefix":"10.5858","volume":"147","author":[{"given":"Luka","family":"Brcic","sequence":"first","affiliation":[{"name":"From the Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria (Brcic, Gallob)"},{"name":"The Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada (Churg)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nolwenn","family":"Le Stang","sequence":"additional","affiliation":[{"name":"MESOPATH College, MESONAT, MESOBANK, Department of BioPathology Centre L\u00e9on B\u00e9rard, Lyon, France (Le Stang, Sequeiros, Karanian, Galateau-Salle)"},{"name":"The Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada (Churg)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Gallob","sequence":"additional","affiliation":[{"name":"From the Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria (Brcic, Gallob)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Pissaloux","sequence":"additional","affiliation":[{"name":"The Unit of Molecular Pathology, INSERM 1052, CNRS 5286 of Cancer Research Center of Lyon, and Team Genetics, Epigenetics and Biology of Sarcomas, Universit\u00e9 Claude Bernard Lyon 1, Lyon, France (Pissaloux, Paindavoine, Tirode, Galateau-Salle)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Sequeiros","sequence":"additional","affiliation":[{"name":"MESOPATH College, MESONAT, MESOBANK, Department of BioPathology Centre L\u00e9on B\u00e9rard, Lyon, France (Le Stang, Sequeiros, Karanian, Galateau-Salle)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Paindavoine","sequence":"additional","affiliation":[{"name":"The Unit of Molecular Pathology, INSERM 1052, CNRS 5286 of Cancer Research Center of Lyon, and Team Genetics, Epigenetics and Biology of Sarcomas, Universit\u00e9 Claude Bernard Lyon 1, Lyon, France (Pissaloux, Paindavoine, Tirode, Galateau-Salle)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean Claude","family":"Pairon","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine and CHI Creteil, Service de Pathologies Professionnelles et de l'Environnement, IST-PE, INSERM, UPEC, Creteil, France (Pairon)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie","family":"Karanian","sequence":"additional","affiliation":[{"name":"MESOPATH College, MESONAT, MESOBANK, Department of BioPathology Centre L\u00e9on B\u00e9rard, Lyon, France (Le Stang, Sequeiros, Karanian, Galateau-Salle)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanja","family":"Dacic","sequence":"additional","affiliation":[{"name":"The Department of Pathology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (Dacic)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Girard","sequence":"additional","affiliation":[{"name":"EURACAN and Institute du Thorax Curie-Montsouris, Institut Curie, Paris, France (Girard)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Churg","sequence":"additional","affiliation":[{"name":"The Department of Pathology, Vancouver General Hospital, Vancouver, British Columbia, Canada (Churg)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Tirode","sequence":"additional","affiliation":[{"name":"The Unit of Molecular Pathology, INSERM 1052, CNRS 5286 of Cancer Research Center of Lyon, and Team Genetics, Epigenetics and Biology of Sarcomas, Universit\u00e9 Claude Bernard Lyon 1, Lyon, France (Pissaloux, Paindavoine, Tirode, Galateau-Salle)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francoise","family":"Galateau-Salle","sequence":"additional","affiliation":[{"name":"MESOPATH College, MESONAT, MESOBANK, Department of BioPathology Centre L\u00e9on B\u00e9rard, Lyon, France (Le Stang, Sequeiros, Karanian, Galateau-Salle)"},{"name":"The Unit of Molecular Pathology, INSERM 1052, CNRS 5286 of Cancer Research Center of Lyon, and Team Genetics, Epigenetics and Biology of Sarcomas, Universit\u00e9 Claude Bernard Lyon 1, Lyon, France (Pissaloux, Paindavoine, Tirode, Galateau-Salle)"},{"name":"Facult\u00e9 de M\u00e9decine and CHI Creteil, Service de Pathologies Professionnelles et de l'Environnement, IST-PE, INSERM, UPEC, Creteil, France (Pairon)"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"3906","published-online":{"date-parts":[[2022,6,23]]},"reference":[{"key":"2023022718565270400_","doi-asserted-by":"crossref","unstructured":"Gemba K, Fujimoto N, Aoe K, et al. 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