Deletions of CDKN2A and MTAP Detected by Copy-Number Variation Array Are Associated with Loss of p16 and MTAP Protein in Pleural Mesothelioma
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...
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| Veröffentlicht in: | Cancers 2023-10, Vol.15 (20), p.4978 |
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| creator | Vrugt, Bart Kirschner, Michaela B. Meerang, Mayura Oehl, Kathrin Wagner, Ulrich Soltermann, Alex Moch, Holger Opitz, Isabelle Wild, Peter J. |
| description | 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’s 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 < 0.0001, and kappa = 0.787, p < 0.0001 respectively). We recommend combined MTAP and p16 immunohistochemistry to confirm the diagnosis of PM. |
| doi_str_mv | 10.3390/cancers15204978 |
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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’s 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 < 0.0001, and kappa = 0.787, p < 0.0001 respectively). We recommend combined MTAP and p16 immunohistochemistry to confirm the diagnosis of PM.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers15204978</identifier><identifier>PMID: 37894345</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Arrays ; Biopsy ; CDKN2A gene ; Cloning ; Cyclin-dependent kinases ; Diagnosis ; Fluorescence in situ hybridization ; Gene deletion ; Genes ; Genomes ; Immunohistochemistry ; Kinases ; Mesothelioma ; Protein expression ; Proteins ; Statistical analysis</subject><ispartof>Cancers, 2023-10, Vol.15 (20), p.4978</ispartof><rights>2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). 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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’s 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 < 0.0001, and kappa = 0.787, p < 0.0001 respectively). We recommend combined MTAP and p16 immunohistochemistry to confirm the diagnosis of PM.</description><subject>Arrays</subject><subject>Biopsy</subject><subject>CDKN2A gene</subject><subject>Cloning</subject><subject>Cyclin-dependent kinases</subject><subject>Diagnosis</subject><subject>Fluorescence in situ hybridization</subject><subject>Gene deletion</subject><subject>Genes</subject><subject>Genomes</subject><subject>Immunohistochemistry</subject><subject>Kinases</subject><subject>Mesothelioma</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Statistical analysis</subject><issn>2072-6694</issn><issn>2072-6694</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkc1u3CAURlHVqonSrLtF6qYbN8C1MV5V1kz_1Ekyi6RbhJnrDpFtpoBbzUPkncM0UdIGIUBwOPrgEvKWsw8ADTuzZrIYIq8EK5tavSDHgtWikLIpX_6zPiKnMd6w3AB4LevX5Ahq1ZRQVsfkdokDJuenSH1PF8vvF6KlZtrQ86t2TZeY0Cbc0G5PF363Ly7mscNAf5jgzOEWbUMw-zwibWP0Nu9m-o9LW7ry8a9zx-WTcB18QjfR3NcDzsEM9ByjT1scnB_NG_KqN0PE04f5hFx__nS1-FqsLr98W7SrwkLTpMKyHhhWqpKmQajUpq-5MhUgs1Z20krVSQDLmIRSobElRyEEKq56Jmqh4IR8vPfu5m7EjcUp5Sh6F9xowl574_T_J5Pb6p_-t-ZMsko1MhvePxiC_zVjTHp00eIwmAn9HLVQKgerQImMvnuG3vg5TPl9B0oAsFIeIp3dUzbkjwvYP6bhTB_KrZ-VG-4Ai3KcPQ</recordid><startdate>20231013</startdate><enddate>20231013</enddate><creator>Vrugt, Bart</creator><creator>Kirschner, Michaela B.</creator><creator>Meerang, Mayura</creator><creator>Oehl, Kathrin</creator><creator>Wagner, Ulrich</creator><creator>Soltermann, Alex</creator><creator>Moch, Holger</creator><creator>Opitz, Isabelle</creator><creator>Wild, Peter J.</creator><general>MDPI AG</general><general>MDPI</general><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7T5</scope><scope>7TO</scope><scope>7XB</scope><scope>8FE</scope><scope>8FH</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M2O</scope><scope>M7P</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7986-2839</orcidid><orcidid>https://orcid.org/0000-0002-1751-5866</orcidid><orcidid>https://orcid.org/0000-0002-5546-3120</orcidid><orcidid>https://orcid.org/0000-0002-1017-3744</orcidid><orcidid>https://orcid.org/0000-0001-7444-9829</orcidid><orcidid>https://orcid.org/0000-0001-5900-9040</orcidid></search><sort><creationdate>20231013</creationdate><title>Deletions of CDKN2A and MTAP Detected by Copy-Number Variation Array Are Associated with Loss of p16 and MTAP Protein in Pleural Mesothelioma</title><author>Vrugt, Bart ; 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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’s 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 < 0.0001, and kappa = 0.787, p < 0.0001 respectively). We recommend combined MTAP and p16 immunohistochemistry to confirm the diagnosis of PM.</abstract><cop>Basel</cop><pub>MDPI AG</pub><pmid>37894345</pmid><doi>10.3390/cancers15204978</doi><orcidid>https://orcid.org/0000-0002-7986-2839</orcidid><orcidid>https://orcid.org/0000-0002-1751-5866</orcidid><orcidid>https://orcid.org/0000-0002-5546-3120</orcidid><orcidid>https://orcid.org/0000-0002-1017-3744</orcidid><orcidid>https://orcid.org/0000-0001-7444-9829</orcidid><orcidid>https://orcid.org/0000-0001-5900-9040</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central Open Access; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | Arrays Biopsy CDKN2A gene Cloning Cyclin-dependent kinases Diagnosis Fluorescence in situ hybridization Gene deletion Genes Genomes Immunohistochemistry Kinases Mesothelioma Protein expression Proteins Statistical analysis |
| title | Deletions of CDKN2A and MTAP Detected by Copy-Number Variation Array Are Associated with Loss of p16 and MTAP Protein in Pleural Mesothelioma |
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