PMID- 25047676
OWN - NLM
STAT- MEDLINE
DCOM- 20150511
LR  - 20220330
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 85
IP  - 3
DP  - 2014 Sep
TI  - HER2 status in lung adenocarcinoma: a comparison of immunohistochemistry, 
      fluorescence in situ hybridization (FISH), dual-ISH, and gene mutations.
PG  - 373-8
LID - S0169-5002(14)00265-7 [pii]
LID - 10.1016/j.lungcan.2014.06.007 [doi]
AB  - OBJECTIVES: While novel anti-human epidermal growth factor receptor 2 (HER2) 
      agents have recently been developed, no definite criteria have been proposed as 
      indications for the use of these agents in patients with lung cancer. Here, we 
      tested HER2 alterations by using four methods and explored the concordance of 
      these methods to improve our understanding of the accuracy of HER2 testing 
      methods. MATERIALS AND METHODS: We analyzed HER2 protein expression by 
      immunohistochemistry (IHC) and HER2 amplification by fluorescence in situ 
      hybridization (FISH) and dual in situ hybridization (DISH) by using a tissue 
      microarray comprising lung adenocarcinoma specimens from 243 consecutive 
      patients. The presence of mutations in the EGFR, KRAS, and HER2 genes were also 
      determined. RESULTS: Positive IHC (score 3+) was observed in six cases (2.5%). 
      Amplification of HER2 was observed in five cases (2.1%) by FISH and in nine cases 
      (3.7%) by DISH. HER2 expression by IHC and gene amplification by FISH were 
      significantly associated (P<0.001). The overall concordance between FISH and DISH 
      by amplification status was 96.7% (P<0.001). One hundred nine tumors (49.9%) had 
      EGFR mutations, 25 (11.2%) had KRAS mutations, and six (2.7%) had HER2 mutations. 
      All of these mutations were mutually exclusive. Cases having HER2 mutations were 
      positively correlated with cases having HER2 amplification (P<0.001). Two of six 
      cases with HER2 mutations showed amplifications by FISH and DISH tests. 
      CONCLUSION: HER2 protein overexpression, gene amplification, and gene mutations 
      appeared to be uncommon in lung adenocarcinoma. Cases with HER2 mutations tended 
      to show HER2 gene amplification. The results indicated that HER2 gene 
      amplification and mutations should be tested to determine whether patients are 
      eligible for administration of new anti-HER2 agents. In addition, DISH was better 
      than FISH for detection of cases with HER2 amplification.
CI  - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved.
FAU - Yoshizawa, Akihiko
AU  - Yoshizawa A
AD  - Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan; 
      Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan. 
      Electronic address: akyoshi@shinshu-u.ac.jp.
FAU - Sumiyoshi, Shinji
AU  - Sumiyoshi S
AD  - Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
FAU - Sonobe, Makoto
AU  - Sonobe M
AD  - Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan.
FAU - Kobayashi, Masashi
AU  - Kobayashi M
AD  - Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan.
FAU - Uehara, Takeshi
AU  - Uehara T
AD  - Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Japan.
FAU - Fujimoto, Masakazu
AU  - Fujimoto M
AD  - Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
FAU - Tsuruyama, Tatsuaki
AU  - Tsuruyama T
AD  - Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
FAU - Date, Hiroshi
AU  - Date H
AD  - Department of Thoracic Surgery, Kyoto University Hospital, Kyoto, Japan.
FAU - Haga, Hironori
AU  - Haga H
AD  - Department of Diagnostic Pathology, Kyoto University Hospital, Kyoto, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140707
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Adenocarcinoma/diagnosis/*genetics/*metabolism
MH  - Adenocarcinoma of Lung
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - ErbB Receptors/genetics
MH  - Female
MH  - Gene Amplification
MH  - Gene Expression
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/diagnosis/*genetics/*metabolism
MH  - Male
MH  - Middle Aged
MH  - *Mutation
MH  - Neoplasm Grading
MH  - Neoplasm Staging
MH  - Proto-Oncogene Proteins p21(ras)/genetics
MH  - Receptor, ErbB-2/*genetics/*metabolism
MH  - Risk Factors
MH  - Tumor Burden
MH  - Young Adult
OTO - NOTNLM
OT  - Dual in situ hybridization
OT  - Fluorescence in situ hybridization
OT  - Human epidermal growth factor receptor 2
OT  - Immunohistochemistry
OT  - Lung adenocarcinoma
OT  - Trastuzumab
EDAT- 2014/07/23 06:00
MHDA- 2015/05/12 06:00
CRDT- 2014/07/23 06:00
PHST- 2014/04/08 00:00 [received]
PHST- 2014/06/02 00:00 [revised]
PHST- 2014/06/08 00:00 [accepted]
PHST- 2014/07/23 06:00 [entrez]
PHST- 2014/07/23 06:00 [pubmed]
PHST- 2015/05/12 06:00 [medline]
AID - S0169-5002(14)00265-7 [pii]
AID - 10.1016/j.lungcan.2014.06.007 [doi]
PST - ppublish
SO  - Lung Cancer. 2014 Sep;85(3):373-8. doi: 10.1016/j.lungcan.2014.06.007. Epub 2014 
      Jul 7.