PMID- 28038708 OWN - NLM STAT- MEDLINE DCOM- 20170306 LR - 20220419 IS - 1532-8198 (Electronic) IS - 1092-9134 (Linking) VI - 26 DP - 2017 Feb TI - Usefulness of p16/CDKN2A fluorescence in situ hybridization and BAP1 immunohistochemistry for the diagnosis of biphasic mesothelioma. PG - 31-37 LID - S1092-9134(16)30217-9 [pii] LID - 10.1016/j.anndiagpath.2016.10.010 [doi] AB - Malignant mesothelioma is a highly aggressive neoplasm, and the histologic subtype is one of the most reliable prognostic factors. Some biphasic mesotheliomas are difficult to distinguish from epithelioid mesotheliomas with atypical fibrous stroma. The aim of this study was to analyze p16/CDKN2A deletions in mesotheliomas by fluorescence in situ hybridization (FISH) and BAP1 immunohistochemistry to evaluate their potential role in the diagnosis of biphasic mesothelioma. We collected 38 cases of pleural mesotheliomas. The results of this study clearly distinguished 29 cases of biphasic mesothelioma from 9 cases of epithelioid mesothelioma. The proportion of biphasic mesotheliomas with homozygous deletions of p16/CDKN2A in total was 96.6% (28/29). Homozygous deletion of p16/CDKN2A was observed in 18 (94.7%) of 19 biphasic mesotheliomas with 100% concordance of the p16/CDKN2A deletion status between the epithelioid and sarcomatoid components in each case. Homozygous deletion of the p16/CDKN2A was observed in 7 (77.8%) of 9 epithelioid mesotheliomas but not in fibrous stroma. BAP1 loss was observed in 5 (38.5%) of 13 biphasic mesotheliomas and in both epithelioid and sarcomatoid components. BAP1 loss was observed in 5 (62.5%) of 8 epithelioid mesotheliomas but not in fibrous stroma. Homozygous deletion of p16/CDKN2A is common in biphasic mesotheliomas, and the analysis of only one component of mesothelioma is sufficient to show that the tumor is malignant. However, compared with histology alone, FISH analysis of the p16/CDKN2A status and BAP1 immunohistochemistry in the spindled mesothelium provide a more objective means to differentiate between biphasic mesothelioma and epithelioid mesothelioma with atypical stromal cells. CI - Copyright (c) 2016 Elsevier Inc. All rights reserved. FAU - Wu, Di AU - Wu D AD - Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, Owada-Shinden 477-96, Yachiyo, Chiba 276-8524, Japan. Electronic address: wu.dier@twmu.ac.jp. FAU - Hiroshima, Kenzo AU - Hiroshima K AD - Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, Owada-Shinden 477-96, Yachiyo, Chiba 276-8524, Japan. Electronic address: hiroshima.kenzo@twmu.ac.jp. FAU - Yusa, Toshikazu AU - Yusa T AD - Department of General Thoracic Surgery and Asbestos Disease Center, Chiba Rosai Hospital, Tatsumidai-higashi 2-16, Ichihara 290-0003, Japan. Electronic address: toshikazu_yusa@chibah.johas.go.jp. FAU - Ozaki, Daisuke AU - Ozaki D AD - Department of Pathology, Chiba Rosai Hospital, Tatsumidai-higashi 2-16, Ichihara 290-0003, Japan. Electronic address: oz-d@umin.ac.jp. FAU - Koh, Eitetsu AU - Koh E AD - Department of Thoracic Surgery, Tokyo Women's Medical University Yachiyo Medical Center, Owada-Shinden 477-96, Yachiyo, Chiba 276-8524, Japan. Electronic address: eitetsuk@gmail.com. FAU - Sekine, Yasuo AU - Sekine Y AD - Department of Thoracic Surgery, Tokyo Women's Medical University Yachiyo Medical Center, Owada-Shinden 477-96, Yachiyo, Chiba 276-8524, Japan. Electronic address: sekine.yasuo@twmu.ac.jp. FAU - Matsumoto, Shinji AU - Matsumoto S AD - Department of Pathology, Fukuoka University School of Medicine and Hospital, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan. Electronic address: matsu@minf.med.fukuoka-u.ac.jp. FAU - Nabeshima, Kazuki AU - Nabeshima K AD - Department of Pathology, Fukuoka University School of Medicine and Hospital, Nanakuma 7-45-1, Jonan-ku, Fukuoka 814-0180, Japan. Electronic address: kaznabes@fukuoka-u.ac.jp. FAU - Sato, Ayuko AU - Sato A AD - Department of Pathology, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo 663-8501, Japan. Electronic address: asato@hyo-med.ac.jp. FAU - Tsujimura, Tohru AU - Tsujimura T AD - Department of Pathology, Hyogo College of Medicine, Mukogawa-cho 1-1, Nishinomiya, Hyogo 663-8501, Japan. Electronic address: tohru@hyo-med.ac.jp. FAU - Yamakawa, Hisami AU - Yamakawa H AD - Department of Thoracic Surgery, Yarita Hospital, Goi 899, Ichihara 290-0056, Japan. Electronic address: hisa46ym@za2.so-net.ne.jp. FAU - Tada, Yuji AU - Tada Y AD - Department of Respirology, Graduate School of Medicine, Chiba University, Inohana 1-8-1, Chuo-ku, Chiba 260-8670, Japan. Electronic address: ytada@faculty.chiba-u.jp. FAU - Shimada, Hideaki AU - Shimada H AD - Department of Surgery, School of Medicine, Toho University, Omorinishi 6-11-1, Ota-ku, Tokyo 143-8541, Japan. Electronic address: hideaki.shimada@med.toho-u.ac.jp. FAU - Tagawa, Masatoshi AU - Tagawa M AD - Division of Pathology and Cell Therapy, Chiba Cancer Center Research Institute, Nitona 666-2, Chuo-ku, Chiba, Chiba 260-8717, Japan. Electronic address: mtagawa@chiba-cc.jp. LA - eng PT - Journal Article DEP - 20161022 PL - United States TA - Ann Diagn Pathol JT - Annals of diagnostic pathology JID - 9800503 RN - 0 (BAP1 protein, human) RN - 0 (Biomarkers, Tumor) RN - 0 (CDKN2A protein, human) RN - 0 (Cyclin-Dependent Kinase Inhibitor p16) RN - 0 (Cyclin-Dependent Kinase Inhibitor p18) RN - 0 (Tumor Suppressor Proteins) RN - EC 3.4.19.12 (Ubiquitin Thiolesterase) SB - IM MH - Aged MH - Biomarkers, Tumor/analysis MH - Cyclin-Dependent Kinase Inhibitor p16 MH - Cyclin-Dependent Kinase Inhibitor p18/*genetics MH - Diagnosis, Differential MH - Female MH - Humans MH - Immunohistochemistry/methods MH - In Situ Hybridization, Fluorescence/methods MH - Male MH - Mesothelioma/*diagnosis/*genetics MH - Middle Aged MH - Pleural Neoplasms/*diagnosis/genetics MH - Tumor Suppressor Proteins/*genetics MH - Ubiquitin Thiolesterase/*genetics OTO - NOTNLM OT - Fluorescence in situ hybridization OT - Mesothelioma OT - p16 EDAT- 2017/01/01 06:00 MHDA- 2017/03/07 06:00 CRDT- 2017/01/01 06:00 PHST- 2016/08/25 00:00 [received] PHST- 2016/10/12 00:00 [revised] PHST- 2016/10/17 00:00 [accepted] PHST- 2017/01/01 06:00 [entrez] PHST- 2017/01/01 06:00 [pubmed] PHST- 2017/03/07 06:00 [medline] AID - S1092-9134(16)30217-9 [pii] AID - 10.1016/j.anndiagpath.2016.10.010 [doi] PST - ppublish SO - Ann Diagn Pathol. 2017 Feb;26:31-37. doi: 10.1016/j.anndiagpath.2016.10.010. Epub 2016 Oct 22.