{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T17:47:11Z","timestamp":1791049631431,"version":"4.1.0"},"reference-count":33,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T00:00:00Z","timestamp":1611532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005610","name":"Fukuoka University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005610","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Cytopathology"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Malignant pleural mesothelioma (MPM) is characterized by mutations in several genes, including cyclin\u2010dependent kinase\u2010inhibitor 2A\/p16 in the 9p21 locus, BRCA1\u2010associated protein 1 (<jats:italic>BAP1<\/jats:italic>), and neurofibromatosis type 2 (<jats:italic>NF2<\/jats:italic>) in the 22q12 locus. Recent studies indicate that fluorescence in situ hybridization (FISH) detects hemizygous loss of <jats:italic>NF2<\/jats:italic> in tissue specimens of MPM. The authors investigated whether <jats:italic>NF2<\/jats:italic> FISH, either alone or in combination with other diagnostic assays (9p21 FISH, methylthioadenosine phosphorylase [MTAP] immunohistochemistry [IHC], and BAP1 IHC), effectively distinguishes MPM cells from reactive mesothelial cells (RMCs) in cell blocks prepared from pleural effusions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>FISH assays were used to examine the deletion status of <jats:italic>NF2<\/jats:italic> and 9p21, and IHC was used to determine the expression of MTAP and BAP1 in cell blocks from 54 cases with MPM and 18 cases with RMCs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Hemizygous <jats:italic>NF2<\/jats:italic> loss (chromosome 22 monosomy or hemizygous deletion) showed 51.9% sensitivity (48.1% for chromosome 22 monosomy and 3.7% for hemizygous deletion) and 100% specificity in differentiating MPM cells from RMCs. Combinations of <jats:italic>NF2<\/jats:italic> FISH, 9p21 FISH, and BAP1 IHC assays yielded greater sensitivity (98.1%) than any assay alone (9p21 FISH, 61.1%; MTAP IHC, 52.8%; or BAP1 IHC, 60.4%). The level of hemizygous <jats:italic>NF2<\/jats:italic> loss in cell blocks positively correlated with that in corresponding tissues. Furthermore, to overcome cytologic specimen\u2010specific challenges, FISH combined with cytokeratin AE1\/AE3 immunofluorescence was necessary in 25.9% of MPM cases for FISH assessment of predominantly scattered MPM cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p><jats:italic>NF2<\/jats:italic> FISH alone or in combination with other diagnostic assays effectively differentiates MPM cells from RMCs in cell blocks prepared from pleural effusions.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cncy.22409","type":"journal-article","created":{"date-parts":[[2021,1,25]],"date-time":"2021-01-25T17:36:17Z","timestamp":1611596177000},"page":"526-536","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Fluorescence in situ hybridization detection of chromosome 22 monosomy in pleural effusion cytology for the diagnosis of mesothelioma"],"prefix":"10.1002","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8872-8957","authenticated-orcid":false,"given":"Yoshiaki","family":"Kinoshita","sequence":"first","affiliation":[{"name":"Department of Pathology Fukuoka University Hospital and School of Medicine Fukuoka Japan"},{"name":"Department of Respiratory Medicine Fukuoka University Chikushi Hospital and School of Medicine Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-3888","authenticated-orcid":false,"given":"Makoto","family":"Hamasaki","sequence":"additional","affiliation":[{"name":"Department of Pathology Fukuoka University Hospital and School of Medicine Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1566-4681","authenticated-orcid":false,"given":"Shinji","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Pathology Fukuoka University Hospital and School of Medicine Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masayo","family":"Yoshimura","sequence":"additional","affiliation":[{"name":"Department of Pathology Fukuoka University Hospital and School of Medicine Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayuko","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Pathology Hyogo College of Medicine Nishinomiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Tsujimura","sequence":"additional","affiliation":[{"name":"Department of Pathology Hyogo College of Medicine Nishinomiya Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiaki","family":"Kamei","sequence":"additional","affiliation":[{"name":"Pathology and Cytology Center BML Group PCL Japan, Inc Fukuoka 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