PMID- 36442384
OWN - NLM
STAT- MEDLINE
DCOM- 20230127
LR  - 20230214
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 175
DP  - 2023 Jan
TI  - Usefulness of NF2 hemizygous loss detected by fluorescence in situ hybridization 
      in diagnosing pleural mesothelioma in tissue and cytology material: A 
      multi-institutional study.
PG  - 27-35
LID - S0169-5002(22)00686-9 [pii]
LID - 10.1016/j.lungcan.2022.11.013 [doi]
AB  - OBJECTIVES: BAP1, CDKN2A, and NF2 are the most frequently altered genes in 
      pleural mesotheliomas (PM). Discriminating PM from benign mesothelial 
      proliferation (BMP) is sometimes challenging; it is well established that BAP1 
      loss, determined by immunohistochemistry (IHC), and CDKN2A homozygous deletion 
      (HD), determined by fluorescence in situ hybridization (FISH), are useful. 
      However, data regarding the diagnostic utility of NF2 FISH in PM is limited. 
      Thus, we performed a multi-institutional study examining the utility of NF2 
      alterations determined by FISH for diagnosing PM in combination with BAP1 loss 
      and CDKN2A HD. MATERIALS AND METHODS: Multi-institutional PM cases, including 106 
      surgical and 107 cell block samples as well as 37 tissue cases of benign 
      mesothelial proliferation (BMP) and 31 cell block cases with reactive mesothelial 
      cells (RMC), were collected and analyzed using IHC for BAP1 and FISH for CDKN2A 
      and NF2. RESULTS: In PM, NF2 FISH revealed hemizygous loss (HL) in 54.7% of 
      tissue cases (TC) and 49.5% of cell block cases (CBC), with about 90% of HL being 
      monosomy. CDKN2A HD or BAP1 loss were detected in 75.5%/65.4% TC or 63.6%/60% 
      CBC, respectively. BMP or RMC showed no BAP1 loss, CDKN2A HD, or NF2 HL. For 
      discriminating PM from BMP, a combination of BAP1 loss, CDKN2A HD, and NF2 HL 
      yielded enhanced sensitivity of 98.1% TC/94.4% CBC. BAP1 loss, CDKN2A HD, or NF2 
      HL were observed in 69%, 70%, or 58% of epithelioid PM, but in 9%, 91%, or 27% of 
      sarcomatoid PM, respectively. Histotype, histological gradings, and CDKN2A 
      deletion status showed significant differences in overall survival, while BAP1 
      loss and NF2 HL did not. CONCLUSION: NF2 HL, consisting predominantly of 
      monosomy, can be detected by FISH in both TC and CBC of PM, and is effective for 
      distinguishing PM from BMP, especially when combined with BAP1 loss and CDKN2A 
      HD.
CI  - Copyright (c) 2022 Elsevier B.V. All rights reserved.
FAU - Sa-Ngiamwibool, Prakasit
AU  - Sa-Ngiamwibool P
AD  - Department of Pathology, Fukuoka University School of Medicine and Hospital, 
      Fukuoka, Japan; Department of Pathology, Faculty of Medicine, Khon Kaen 
      University, Khon Kean, Thailand.
FAU - Hamasaki, Makoto
AU  - Hamasaki M
AD  - Department of Pathology, Fukuoka University School of Medicine and Hospital, 
      Fukuoka, Japan.
FAU - Kinoshita, Yoshiaki
AU  - Kinoshita Y
AD  - Department of Respiratory Medicine, Fukuoka University Chikushi Hospital, 
      Chikushino, Japan.
FAU - Matsumoto, Shinji
AU  - Matsumoto S
AD  - Department of Pathology, Fukuoka University School of Medicine and Hospital, 
      Fukuoka, Japan.
FAU - Sato, Ayuko
AU  - Sato A
AD  - Department of Molecular Pathology, School of Medicine, Hyogo Medical University, 
      Nishinomiya, Japan.
FAU - Tsujimura, Tohru
AU  - Tsujimura T
AD  - Department of Molecular Pathology, School of Medicine, Hyogo Medical University, 
      Nishinomiya, Japan.
FAU - Kawahara, Kunimitsu
AU  - Kawahara K
AD  - Division of Pathology for Regional Communication, Kobe University Graduate School 
      of Medicine, Kobe, Japan.
FAU - Kasai, Takahiko
AU  - Kasai T
AD  - Department of Pathology, National Hospital Organization Kinki-chuo Chest Medical 
      Center, Osaka, Japan.
FAU - Kushitani, Kei
AU  - Kushitani K
AD  - Department of Pathology, Hiroshima University Graduate School of Biomedical and 
      Health Sciences, Hiroshima, Japan.
FAU - Takeshima, Yukio
AU  - Takeshima Y
AD  - Department of Pathology, Hiroshima University Graduate School of Biomedical and 
      Health Sciences, Hiroshima, Japan.
FAU - Hiroshima, Kenzo
AU  - Hiroshima K
AD  - Department of Pathology, Tokyo Women's Medical University Yachiyo Medical Center, 
      Yachiyo, Japan.
FAU - Iwasaki, Akinori
AU  - Iwasaki A
AD  - Department of Thoracic Surgery, Fukuoka University School of Medicine and 
      Hospital, Fukuoka, Japan.
FAU - Nabeshima, Kazuki
AU  - Nabeshima K
AD  - Department of Pathology, Fukuoka University School of Medicine and Hospital, 
      Fukuoka, Japan. Electronic address: kaznabes@fukuoka-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20221119
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Tumor Suppressor Proteins)
RN  - 0 (NF2 protein, human)
RN  - 0 (Neurofibromin 2)
SB  - IM
MH  - Humans
MH  - Homozygote
MH  - In Situ Hybridization, Fluorescence
MH  - *Lung Neoplasms/pathology
MH  - *Mesothelioma/diagnosis/genetics/pathology
MH  - *Mesothelioma, Malignant/genetics
MH  - *Pleural Neoplasms/diagnosis/genetics/pathology
MH  - Sequence Deletion
MH  - Tumor Suppressor Proteins/genetics
MH  - *Neurofibromin 2/genetics
OTO - NOTNLM
OT  - BAP1
OT  - CDKN2A
OT  - Cell block
OT  - FISH
OT  - NF2
OT  - Pleural mesothelioma
COIS- Declaration of Competing Interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2022/11/29 06:00
MHDA- 2023/01/25 06:00
CRDT- 2022/11/28 18:22
PHST- 2022/08/21 00:00 [received]
PHST- 2022/10/30 00:00 [revised]
PHST- 2022/11/17 00:00 [accepted]
PHST- 2022/11/29 06:00 [pubmed]
PHST- 2023/01/25 06:00 [medline]
PHST- 2022/11/28 18:22 [entrez]
AID - S0169-5002(22)00686-9 [pii]
AID - 10.1016/j.lungcan.2022.11.013 [doi]
PST - ppublish
SO  - Lung Cancer. 2023 Jan;175:27-35. doi: 10.1016/j.lungcan.2022.11.013. Epub 2022 
      Nov 19.