PMID- 31231129
OWN - NLM
STAT- MEDLINE
DCOM- 20210125
LR  - 20230210
IS  - 1530-0285 (Electronic)
IS  - 0893-3952 (Linking)
VI  - 33
IP  - 2
DP  - 2020 Feb
TI  - Hemizygous loss of NF2 detected by fluorescence in situ hybridization is useful 
      for the diagnosis of malignant pleural mesothelioma.
PG  - 235-244
LID - 10.1038/s41379-019-0309-6 [doi]
AB  - Neurofibromatosis type 2 (NF2) gene, a tumor suppressor gene located on 
      chromosome 22q12.2, is frequently abnormal in mesothelioma. Recent studies have 
      revealed the effectiveness of diagnostic assays for differentiating malignant 
      pleural mesothelioma from reactive mesothelial hyperplasia. These include 
      detection of homozygous deletion of the 9p21 locus by fluorescence in situ 
      hybridization (FISH) (9p21 FISH), loss of expression of BAP1 as detected by 
      immunohistochemistry, and loss of expression of methylthioadenosine phosphorylase 
      (MTAP) as detected by immunohistochemistry. However, the application of FISH 
      detection of NF2 gene deletion (NF2 FISH) in differentiation of malignant pleural 
      mesothelioma from reactive mesothelial hyperplasia has not been fully evaluated. 
      In this study, we investigated whether NF2 FISH, either alone or in a combination 
      with other diagnostic assays (9p21 FISH, MTAP immunohistochemistry, and BAP1 
      immunohistochemistry), is effective for distinguishing malignant pleural 
      mesothelioma from reactive mesothelial hyperplasia. This study cohort included 
      malignant pleural mesothelioma (n = 47) and reactive mesothelial hyperplasia 
      cases (n = 27) from a period between 2001 and 2017. We used FISH to examine 
      deletion status of NF2 and 9p21 and immunohistochemistry to examine expression of 
      MTAP and BAP1 in malignant pleural mesothelioma and in reactive mesothelial 
      hyperplasia. Hemizygous NF2 loss (chromosome 22 monosomy or hemizygous deletion) 
      was detected in 25 of 47 (53.2%) mesothelioma cases. None of the mesothelioma 
      cases showed homozygous NF2 deletion. Hemizygous NF2 loss showed 53.2% 
      sensitivity and 100% specificity in differentiating malignant pleural 
      mesothelioma from reactive mesothelial hyperplasia. A combination of NF2 FISH, 
      9p21 FISH, and BAP1 immunohistochemistry yielded greater sensitivity (100%) than 
      that detected for either diagnostic assay alone (53.2% for NF2 FISH, 78.7% for 
      9p21 FISH, 70.2% for MTAP immunohistochemistry, or 57.4% for BAP1 
      immunohistochemistry). Thus, NF2 FISH in combination with other diagnostic assays 
      is effective for distinguishing malignant pleural mesothelioma from reactive 
      mesothelial hyperplasia.
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 Hospital and School of 
      Medicine, Fukuoka, Japan.
FAU - Hamasaki, Makoto
AU  - Hamasaki M
AD  - Department of Pathology, Fukuoka University Hospital and School of Medicine, 
      Fukuoka, Japan.
FAU - Yoshimura, Masayo
AU  - Yoshimura M
AUID- ORCID: 0000-0002-2664-9823
AD  - Department of Pathology, Fukuoka University Hospital and School of Medicine, 
      Fukuoka, Japan.
FAU - Matsumoto, Shinji
AU  - Matsumoto S
AD  - Department of Pathology, Fukuoka University Hospital and School of Medicine, 
      Fukuoka, 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
AD  - Department of Pathology, Fukuoka University Hospital and School of Medicine, 
      Fukuoka, Japan. kaznabes@fukuoka-u.ac.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190623
PL  - United States
TA  - Mod Pathol
JT  - Modern pathology : an official journal of the United States and Canadian Academy 
      of Pathology, Inc
JID - 8806605
RN  - 0 (BAP1 protein, human)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (NF2 protein, human)
RN  - 0 (Neurofibromin 2)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.4.2.1 (Purine-Nucleoside Phosphorylase)
RN  - EC 2.4.2.28 (5'-methylthioadenosine phosphorylase)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/*genetics
MH  - Chromosomes, Human, Pair 9
MH  - Female
MH  - *Gene Deletion
MH  - Genetic Predisposition to Disease
MH  - Hemizygote
MH  - Humans
MH  - Hyperplasia
MH  - Immunohistochemistry
MH  - *In Situ Hybridization, Fluorescence
MH  - Male
MH  - Mesothelioma, Malignant/chemistry/*genetics/mortality/pathology
MH  - Middle Aged
MH  - Neurofibromin 2/*genetics
MH  - Phenotype
MH  - Pleural Neoplasms/chemistry/*genetics/mortality/pathology
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - Purine-Nucleoside Phosphorylase/analysis
MH  - Reproducibility of Results
MH  - Retrospective Studies
MH  - Tumor Suppressor Proteins/analysis
MH  - Ubiquitin Thiolesterase/analysis
EDAT- 2019/06/25 06:00
MHDA- 2021/01/26 06:00
CRDT- 2019/06/25 06:00
PHST- 2019/04/04 00:00 [received]
PHST- 2019/05/27 00:00 [accepted]
PHST- 2019/05/27 00:00 [revised]
PHST- 2019/06/25 06:00 [pubmed]
PHST- 2021/01/26 06:00 [medline]
PHST- 2019/06/25 06:00 [entrez]
AID - S0893-3952(22)00928-0 [pii]
AID - 10.1038/s41379-019-0309-6 [doi]
PST - ppublish
SO  - Mod Pathol. 2020 Feb;33(2):235-244. doi: 10.1038/s41379-019-0309-6. Epub 2019 Jun 
      23.