PMID- 30885343
OWN - NLM
STAT- MEDLINE
DCOM- 20200305
LR  - 20201218
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 130
DP  - 2019 Apr
TI  - Highly expressed EZH2 in combination with BAP1 and MTAP loss, as detected by 
      immunohistochemistry, is useful for differentiating malignant pleural 
      mesothelioma from reactive mesothelial hyperplasia.
PG  - 187-193
LID - S0169-5002(19)30309-5 [pii]
LID - 10.1016/j.lungcan.2019.02.004 [doi]
AB  - OBJECTIVE: Malignant pleural mesothelioma (MPM) is an aggressive neoplasm with 
      poor prognosis. Loss of BRCA-associated protein 1 (BAP1) protein expression as 
      detected by immunohistochemistry (IHC) and homozygous deletion (HD) of the 9p21 
      locus as detected by fluorescence in situ hybridization (FISH) permits 
      differentiation of MPM from reactive mesothelial hyperplasia (RMH). We have 
      previously reported that detecting the loss of methylthioadenosine phosphorylase 
      (MTAP) using IHC is a surrogate assay for 9p21 FISH. Furthermore, enhancer of 
      zeste homolog 2 (EZH2), which encodes a component of polycomb repressor complex 2 
      (PRC-2), has been overexpressed in various tumors as well as MPM. In the current 
      study, we investigated whether EZH2 IHC assay, alone or in combination with BAP1 
      and MTAP IHC, is useful for distinguishing MPM from RMH. MATERIALS AND METHODS: 
      We examined IHC expression of EZH2, BAP1, and MTAP, and 9p21 FISH in MPM (n = 38) 
      and RMH (n = 29) and analyzed the sensitivity and specificity of each detection 
      assay for distinguishing MPM from RMH. RESULTS AND CONCLUSION: EZH2, BAP1, and 
      MTAP IHC, and 9p21 FISH were characterized by a 100% specificity each and 44.7%, 
      52.6%, 47.4%, and 65.8% sensitivities, respectively. A combination of EZH2 and 
      BAP1 IHC, and 9p21 FISH showed the greatest sensitivity (89.5%). Using IHC alone 
      (EZH2, BAP1, and MTAP IHC) also yielded a good sensitivity of 86.9%; this level 
      is high enough for routine diagnostics. There were no statistically significant 
      associations between expression of EZH2 and that of other markers (BAP1 and MTAP 
      IHC) or 9p21 HD. However, a high expression level of EZH2 was significantly 
      associated with short survival (P = 0.025). In conclusion, adding a high 
      expression level of EZH2 to a combination of BAP1 and MTAP loss, all detected by 
      IHC, demonstrated useful for discriminating MPM from RMH.
CI  - Copyright (c) 2019 Elsevier B.V. All rights reserved.
FAU - Yoshimura, Masayo
AU  - Yoshimura M
AD  - Department of Pathology, Fukuoka University School of Medicine and Hospital, 
      Fukuoka, Japan.
FAU - Kinoshita, Yoshiaki
AU  - Kinoshita Y
AD  - Department of Pathology, Fukuoka University School of Medicine and Hospital, 
      Fukuoka, Japan.
FAU - Hamasaki, Makoto
AU  - Hamasaki M
AD  - Department of Pathology, Fukuoka University School of Medicine and Hospital, 
      Fukuoka, Japan.
FAU - Matsumoto, Shinji
AU  - Matsumoto S
AD  - Department of Pathology, Fukuoka University School of Medicine and Hospital, 
      Fukuoka, Japan.
FAU - Hida, Tomoyuki
AU  - Hida T
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Oda, Yoshinao
AU  - Oda Y
AD  - Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, 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  - Research Support, Non-U.S. Gov't
DEP - 20190227
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (BAP1 protein, human)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Tumor Suppressor Proteins)
RN  - EC 2.1.1.43 (EZH2 protein, human)
RN  - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
RN  - EC 3.4.19.12 (Ubiquitin Thiolesterase)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers, Tumor/genetics/*metabolism
MH  - Diagnosis, Differential
MH  - Enhancer of Zeste Homolog 2 Protein/genetics/*metabolism
MH  - Epithelium/*pathology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Hyperplasia/*diagnosis
MH  - Immunohistochemistry
MH  - Lung Neoplasms/*diagnosis
MH  - Male
MH  - Mesothelioma/*diagnosis
MH  - Mesothelioma, Malignant
MH  - Microtubule-Associated Proteins/metabolism
MH  - Middle Aged
MH  - Pleural Neoplasms/*diagnosis
MH  - Sensitivity and Specificity
MH  - Tumor Suppressor Proteins/metabolism
MH  - Ubiquitin Thiolesterase/metabolism
MH  - Up-Regulation
OTO - NOTNLM
OT  - 9p21 Fluorescence in situ hybridization
OT  - BRCA1-associated protein 1
OT  - Enhancer of zeste homolog 2
OT  - Malignant pleural mesothelioma
OT  - Methylthioadenosine phosphorylase
OT  - Reactive mesothelial hyperplasia
EDAT- 2019/03/20 06:00
MHDA- 2020/03/07 06:00
CRDT- 2019/03/20 06:00
PHST- 2018/12/13 00:00 [received]
PHST- 2019/01/28 00:00 [revised]
PHST- 2019/02/03 00:00 [accepted]
PHST- 2019/03/20 06:00 [entrez]
PHST- 2019/03/20 06:00 [pubmed]
PHST- 2020/03/07 06:00 [medline]
AID - S0169-5002(19)30309-5 [pii]
AID - 10.1016/j.lungcan.2019.02.004 [doi]
PST - ppublish
SO  - Lung Cancer. 2019 Apr;130:187-193. doi: 10.1016/j.lungcan.2019.02.004. Epub 2019 
      Feb 27.