{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chapel DB"],"funding":["NIBIB NIH HHS","U.S. Department of Health & Human Services | NIH | National Cancer Institute","U.S. Department of Defense","NCI NIH HHS","Ovarian Cancer Research Fund Alliance"],"pagination":["1383-1397"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9529776"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["35(10)"],"pubmed_abstract":["BAP1 and MTAP immunostains play an important role in diagnosis of mesothelioma, but additional markers are needed to increase sensitivity. We analyzed 84 pleural mesotheliomas (51 epithelioid, 27 biphasic, 6 sarcomatoid) by a hybrid-capture next-generation sequencing (NGS) panel including complete coverage of coding and splicing regions for BAP1, CDKN2A/MTAP, NF2, and TP53 and correlated molecular findings with diagnostic immunostains for BAP1, MTAP, Merlin, and p53, respectively. Fifty-seven reactive mesothelial proliferations served as benign comparators. Loss of BAP1, MTAP, and Merlin protein expression were, respectively, 54%, 46%, and 52% sensitive and 100% specific for mesothelioma. Two-marker immunopanels of BAP1 + MTAP, BAP1 + Merlin, and MTAP + Merlin were 79%, 85%, and 71% sensitive for mesothelioma, while a three-marker immunopanel of BAP1 + MTAP + Merlin was 90% sensitive. Diffuse (mutant-pattern) p53 immunostaining was seen in only 6 (7%) tumors but represented the only immunohistochemical abnormality in 2 cases. Null-pattern p53 was not specific for malignancy. An immunopanel of BAP1 + MTAP + Merlin + p53 was 93% sensitive for mesothelioma, and panel NGS detected a pathogenic alteration in BAP1, MTAP, NF2, and/or TP53 in 95%. Together, 83 (99%) of 84 tumors showed a diagnostic alteration by either immunohistochemistry or panel NGS. Adding Merlin to the standard BAP1 + MTAP immunopanel increases sensitivity for mesothelioma without sacrificing specificity. p53 immunohistochemistry and panel NGS with complete coverage of BAP1, CDKN2A/MTAP, TP53, and NF2 may be useful in diagnostically challenging cases."],"journal":["Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc"],"pubmed_title":["Clinical and molecular validation of BAP1, MTAP, P53, and Merlin immunohistochemistry in diagnosis of pleural mesothelioma."],"pmcid":["PMC9529776"],"funding_grant_id":["W81XWH-17-1-0373","RO1 CA120528-12","650320","R01 CA120528","R01 EB025964"],"pubmed_authors":["Bueno R","Sholl LM","Barlow J","Chapel DB","Hornick JL"],"additional_accession":[]},"is_claimable":false,"name":"Clinical and molecular validation of BAP1, MTAP, P53, and Merlin immunohistochemistry in diagnosis of pleural mesothelioma.","description":"BAP1 and MTAP immunostains play an important role in diagnosis of mesothelioma, but additional markers are needed to increase sensitivity. We analyzed 84 pleural mesotheliomas (51 epithelioid, 27 biphasic, 6 sarcomatoid) by a hybrid-capture next-generation sequencing (NGS) panel including complete coverage of coding and splicing regions for BAP1, CDKN2A/MTAP, NF2, and TP53 and correlated molecular findings with diagnostic immunostains for BAP1, MTAP, Merlin, and p53, respectively. Fifty-seven reactive mesothelial proliferations served as benign comparators. Loss of BAP1, MTAP, and Merlin protein expression were, respectively, 54%, 46%, and 52% sensitive and 100% specific for mesothelioma. Two-marker immunopanels of BAP1 + MTAP, BAP1 + Merlin, and MTAP + Merlin were 79%, 85%, and 71% sensitive for mesothelioma, while a three-marker immunopanel of BAP1 + MTAP + Merlin was 90% sensitive. Diffuse (mutant-pattern) p53 immunostaining was seen in only 6 (7%) tumors but represented the only immunohistochemical abnormality in 2 cases. Null-pattern p53 was not specific for malignancy. An immunopanel of BAP1 + MTAP + Merlin + p53 was 93% sensitive for mesothelioma, and panel NGS detected a pathogenic alteration in BAP1, MTAP, NF2, and/or TP53 in 95%. Together, 83 (99%) of 84 tumors showed a diagnostic alteration by either immunohistochemistry or panel NGS. Adding Merlin to the standard BAP1 + MTAP immunopanel increases sensitivity for mesothelioma without sacrificing specificity. p53 immunohistochemistry and panel NGS with complete coverage of BAP1, CDKN2A/MTAP, TP53, and NF2 may be useful in diagnostically challenging cases.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2026-06-04T04:54:16.232Z","creation":"2025-02-19T04:20:26.385Z"},"accession":"S-EPMC9529776","cross_references":{"pubmed":["35459788"],"doi":["10.1038/s41379-022-01081-z"]}}