{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T02:40:24Z","timestamp":1791945624322,"version":"4.3.4"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T00:00:00Z","timestamp":1602720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"The National Cancer Institute","doi-asserted-by":"publisher","award":["NCI 2 R01 CA120528\u201011A1"],"award-info":[{"award-number":["NCI 2 R01 CA120528\u201011A1"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2021,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    <jats:italic>BRCA1\u2010associated protein\u20101<\/jats:italic>\n                    (\n                    <jats:italic>BAP1<\/jats:italic>\n                    ) expression is commonly lost in several tumors including malignant pleural mesothelioma (MPM). Presence or absence of immunohistochemical BAP1 nuclear staining in tumor cells is currently used for differential diagnosis of MPM. In this study, a large cohort of 596 MPM tumors with available clinical data was analyzed to examine associations of BAP1 staining pattern with clinical and molecular features that may reflect the impact of\n                    <jats:italic>BAP1<\/jats:italic>\n                    mutation on MPM biology. Cases were classified according to the BAP1 staining pattern of tumor cells. Exome and RNA\u2010sequencing data were available for subsets of cases. Levels of mRNA encoding claudin 15 (\n                    <jats:italic>CLDN15<\/jats:italic>\n                    ) and vimentin (\n                    <jats:italic>VIM<\/jats:italic>\n                    ) were determined using RT\u2010qPCR on 483 cases to estimate the relative proportions of epithelial\u2010like and mesenchymal\u2010like components in each tumor. Four BAP1 staining patterns were observed: single\u2010pattern nuclear staining (36%), single\u2010pattern cytoplasmic staining (25%), single\u2010pattern absent staining (12%), and combinations of these staining patterns (27%). This study confirmed prior reports that nuclear BAP1 is more frequently associated with wild\u2010type\n                    <jats:italic>BAP1<\/jats:italic>\n                    and sarcomatoid histology. However, no associations between BAP1 staining pattern(s) and mutations in specific protein domains and\/or mutation type were observed. BAP1 staining patterns were significantly associated (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) with\n                    <jats:italic>BAP1<\/jats:italic>\n                    gene expression, MPM histologic subtypes, molecular clusters, and markers of epithelial\u2010to\u2010mesenchymal transition. Frequent observation of combinations of BAP1 staining patterns in MPM tumors indicated intra\u2010tumoral heterogeneity of\n                    <jats:italic>BAP1<\/jats:italic>\n                    status. Cytoplasmic BAP1 staining was identified as a putative indicator of favorable prognosis in non\u2010epithelioid MPM. In conclusion, novel significant associations among different BAP1 staining patterns and subgroups of MPM tumors were observed, suggesting that the role of\n                    <jats:italic>BAP1<\/jats:italic>\n                    in tumor progression may be more complex than its presumed tumor suppressor function. Cytoplasmic staining was identified as a putative indicator of favorable prognosis in non\u2010epithelioid MPM, potentially addressing a critical need in clinical decision\u2010making in this disease. \u00a9 2020 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.5551","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T01:31:20Z","timestamp":1600392680000},"page":"68-79","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Large\u2010scale analysis of\n                    <scp>BAP1<\/scp>\n                    expression reveals novel associations with clinical and molecular features of malignant pleural mesothelioma"],"prefix":"10.1002","volume":"253","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4397-9805","authenticated-orcid":false,"given":"Assunta","family":"De Rienzo","sequence":"first","affiliation":[{"name":"The Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center Brigham and Women's Hospital, and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4383-6938","authenticated-orcid":false,"given":"Lucian R","family":"Chirieac","sequence":"additional","affiliation":[{"name":"Department of Pathology Brigham and Women's Hospital, and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8568-1591","authenticated-orcid":false,"given":"Yin P","family":"Hung","sequence":"additional","affiliation":[{"name":"Department of Pathology Massachusetts General Hospital and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David T","family":"Severson","sequence":"additional","affiliation":[{"name":"The Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center Brigham and Women's Hospital, and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Freyaldenhoven","sequence":"additional","affiliation":[{"name":"The Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center Brigham and Women's Hospital, and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne E","family":"Gustafson","sequence":"additional","affiliation":[{"name":"The Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center Brigham and Women's Hospital, and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhien T","family":"Dao","sequence":"additional","affiliation":[{"name":"The Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center Brigham and Women's Hospital, and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire V","family":"Meyerovitz","sequence":"additional","affiliation":[{"name":"The Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center Brigham and Women's Hospital, and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michela E","family":"Oster","sequence":"additional","affiliation":[{"name":"The Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center Brigham and Women's Hospital, and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3055-4296","authenticated-orcid":false,"given":"Roderick V","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences Virginia Tech  Blacksburg VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beow Y","family":"Yeap","sequence":"additional","affiliation":[{"name":"Department of Medicine Massachusetts General Hospital and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1258-8468","authenticated-orcid":false,"given":"Raphael","family":"Bueno","sequence":"additional","affiliation":[{"name":"The Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center Brigham and Women's Hospital, and Harvard Medical School  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0990-8317","authenticated-orcid":false,"given":"William G","family":"Richards","sequence":"additional","affiliation":[{"name":"The Thoracic Surgery Oncology Laboratory and the International Mesothelioma Program (www.impmeso.org), Division of Thoracic Surgery and the Lung Center Brigham and Women's Hospital, and Harvard Medical School  Boston MA 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