PMID- 33493384
OWN - NLM
STAT- MEDLINE
DCOM- 20220224
LR  - 20220224
IS  - 1934-6638 (Electronic)
IS  - 1934-662X (Linking)
VI  - 129
IP  - 7
DP  - 2021 Jul
TI  - Fluorescence in situ hybridization detection of chromosome 22 monosomy in pleural 
      effusion cytology for the diagnosis of mesothelioma.
PG  - 526-536
LID - 10.1002/cncy.22409 [doi]
AB  - BACKGROUND: Malignant pleural mesothelioma (MPM) is characterized by mutations in 
      several genes, including cyclin-dependent kinase-inhibitor 2A/p16 in the 9p21 
      locus, BRCA1-associated protein 1 (BAP1), and neurofibromatosis type 2 (NF2) in 
      the 22q12 locus. Recent studies indicate that fluorescence in situ hybridization 
      (FISH) detects hemizygous loss of NF2 in tissue specimens of MPM. The authors 
      investigated whether NF2 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. METHODS: FISH assays were used to examine the deletion status of NF2 
      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. RESULTS: Hemizygous NF2 
      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 NF2 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 NF2 loss in cell blocks positively correlated with that in 
      corresponding tissues. Furthermore, to overcome cytologic specimen-specific 
      challenges, FISH combined with cytokeratin AE1/AE3 immunofluorescence was 
      necessary in 25.9% of MPM cases for FISH assessment of predominantly scattered 
      MPM cells. CONCLUSIONS: NF2 FISH alone or in combination with other diagnostic 
      assays effectively differentiates MPM cells from RMCs in cell blocks prepared 
      from pleural effusions.
CI  - (c) 2021 American Cancer Society.
FAU - Kinoshita, Yoshiaki
AU  - Kinoshita Y
AUID- ORCID: 0000-0002-8872-8957
AD  - Department of Pathology, Fukuoka University Hospital and School of Medicine, 
      Fukuoka, Japan.
AD  - Department of Respiratory Medicine, Fukuoka University Chikushi Hospital and 
      School of Medicine, Fukuoka, Japan.
FAU - Hamasaki, Makoto
AU  - Hamasaki M
AUID- ORCID: 0000-0002-2481-3888
AD  - Department of Pathology, Fukuoka University Hospital and School of Medicine, 
      Fukuoka, Japan.
FAU - Matsumoto, Shinji
AU  - Matsumoto S
AUID- ORCID: 0000-0002-1566-4681
AD  - Department of Pathology, Fukuoka University Hospital and School of Medicine, 
      Fukuoka, Japan.
FAU - Yoshimura, Masayo
AU  - Yoshimura M
AD  - Department of Pathology, Fukuoka University Hospital and School of Medicine, 
      Fukuoka, Japan.
FAU - Sato, Ayuko
AU  - Sato A
AD  - Department of Pathology, Hyogo College of Medicine, Nishinomiya, Japan.
FAU - Tsujimura, Tohru
AU  - Tsujimura T
AD  - Department of Pathology, Hyogo College of Medicine, Nishinomiya, Japan.
FAU - Kamei, Toshiaki
AU  - Kamei T
AD  - Pathology and Cytology Center, BML Group PCL Japan, Inc, Fukuoka, Japan.
FAU - Kawahara, Kunimitsu
AU  - Kawahara K
AD  - Department of Pathology, Osaka Habikino Medical Center, Osaka, Japan.
FAU - Iwasaki, Akinori
AU  - Iwasaki A
AD  - Department of Thoracic Surgery, Fukuoka University Hospital and School of 
      Medicine, Fukuoka, Japan.
FAU - Nabeshima, Kazuki
AU  - Nabeshima K
AUID- ORCID: 0000-0002-0691-1222
AD  - Department of Pathology, Fukuoka University Hospital and School of Medicine, 
      Fukuoka, Japan.
LA  - eng
GR  - the Research Center for Advanced Molecular Medicine, Fukuoka University/
GR  - Grants-in-Aid for Scientific Research (#24590495)/the Japanese Society for the 
      Promotion of Science/
GR  - (#171032)/the Central Research Institute of Fukuoka University/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210125
PL  - United States
TA  - Cancer Cytopathol
JT  - Cancer cytopathology
JID - 101499453
RN  - 0 (BAP1 protein, human)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Cyclin-Dependent Kinase Inhibitor p16)
RN  - 0 (NF2 protein, human)
RN  - 0 (Neurofibromin 2)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
SB  - IM
MH  - Biomarkers, Tumor/genetics
MH  - Chromosomes, Human, Pair 22/*genetics
MH  - Cyclin-Dependent Kinase Inhibitor p16
MH  - Humans
MH  - *In Situ Hybridization, Fluorescence
MH  - Mesothelioma, Malignant/*diagnosis/*genetics/pathology
MH  - *Monosomy/diagnosis/genetics/pathology
MH  - Neurofibromin 2/deficiency/genetics
MH  - *Pleural Effusion/diagnosis/genetics/pathology
MH  - *Pleural Neoplasms/diagnosis/genetics/pathology
MH  - Tumor Suppressor Proteins
MH  - Ubiquitin Thiolesterase
OTO - NOTNLM
OT  - fluorescence in situ hybridization
OT  - immunohistochemistry
OT  - mesothelioma
OT  - methylthioadenosine phosphorylase
OT  - neurofibromatosis type 2
OT  - pleural effusion cytology
OT  - reactive mesothelial cells
EDAT- 2021/01/26 06:00
MHDA- 2022/02/25 06:00
CRDT- 2021/01/25 17:18
PHST- 2020/12/17 00:00 [revised]
PHST- 2020/09/05 00:00 [received]
PHST- 2020/12/21 00:00 [accepted]
PHST- 2021/01/26 06:00 [pubmed]
PHST- 2022/02/25 06:00 [medline]
PHST- 2021/01/25 17:18 [entrez]
AID - 10.1002/cncy.22409 [doi]
PST - ppublish
SO  - Cancer Cytopathol. 2021 Jul;129(7):526-536. doi: 10.1002/cncy.22409. Epub 2021 
      Jan 25.