PMID- 27794407
OWN - NLM
STAT- MEDLINE
DCOM- 20171030
LR  - 20220408
IS  - 1872-8332 (Electronic)
IS  - 0169-5002 (Linking)
VI  - 101
DP  - 2016 Nov
TI  - Diagnostic algorithm for detection of targetable driver mutations in lung 
      adenocarcinomas: Comprehensive analyses of 205 cases with immunohistochemistry, 
      real-time PCR and fluorescence in situ hybridization methods.
PG  - 40-47
LID - S0169-5002(16)30473-1 [pii]
LID - 10.1016/j.lungcan.2016.09.007 [doi]
AB  - OBJECTIVES: Analysis of the targetable driver mutations is now recommended in all 
      patients with advanced lung adenocarcinoma. Molecular-based methods are usually 
      adopted, however, along with the implementation of highly sensitive and/or 
      mutation-specific antibodies, immunohistochemistry (IHC) has been considered an 
      alternative method for identifying driver mutations in lung adenocarcinomas. 
      MATERIALS AND METHODS: A total of 205 lung adenocarcinomas were examined for EGFR 
      mutations and ALK and ROS1 rearrangements using real-time PCR, fluorescence in 
      situ hybridization (FISH) and IHC in parallel. The performance of different 
      commercially available IHC antibody clones toward targetable driver mutations was 
      evaluated. The association between these driver mutations and clinicopathological 
      characteristics was also analyzed. RESULTS: In 205 cases we studied, 58.5% were 
      found to harbor EGFR mutations, 6.3% ALK rearrangements and 1.0% ROS1 
      rearrangements. Compared to molecular-based methods, IHC of EGFR mutations showed 
      an excellent specificity but the sensitivity is suboptimal, while IHC of ALK and 
      ROS1 rearrangements demonstrated high sensitivity and specificity. No significant 
      difference regarding the performance of different antibody clones toward these 
      driver mutations was observed, except that clone SP125 showed a higher 
      sensitivity than 43B2 in the detection of p.L858R of EGFR. CONCLUSION: In 
      circumstances such as poor quality of nucleic acids or low content of tumor 
      cells, IHC of EGFR mutation-specific antibodies could be used as an alternative 
      method. Patients negative for EGFR mutations are subjected to further analysis on 
      ALK and ROS1 rearrangements using IHC methods. Herein, we proposed a lung 
      adenocarcinoma testing algorithm for the application of IHC in therapeutic 
      diagnosis.
CI  - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved.
FAU - Kao, Hua-Lin
AU  - Kao HL
AD  - Division of Molecular Pathology, Department of Pathology and Laboratory Medicine, 
      Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, 
      School of Medicine, National Yang-Ming University, Taipei, Taiwan; Department of 
      Pathology and Laboratory Medicine, Cathay General Hospital, Taipei, Taiwan.
FAU - Yeh, Yi-Chen
AU  - Yeh YC
AD  - Division of Molecular Pathology, Department of Pathology and Laboratory Medicine, 
      Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, 
      School of Medicine, National Yang-Ming University, Taipei, Taiwan.
FAU - Lin, Chin-Hsuan
AU  - Lin CH
AD  - Division of Molecular Pathology, Department of Pathology and Laboratory Medicine, 
      Taipei Veterans General Hospital, Taipei, Taiwan; Department of Pathology, 
      Taichung Cheng-Ching Hospital, Taichung, Taiwan.
FAU - Hsu, Wei-Fang
AU  - Hsu WF
AD  - Division of Molecular Pathology, Department of Pathology and Laboratory Medicine, 
      Taipei Veterans General Hospital, Taipei, Taiwan.
FAU - Hsieh, Wen-Yu
AU  - Hsieh WY
AD  - Division of Molecular Pathology, Department of Pathology and Laboratory Medicine, 
      Taipei Veterans General Hospital, Taipei, Taiwan.
FAU - Ho, Hsiang-Ling
AU  - Ho HL
AD  - Division of Molecular Pathology, Department of Pathology and Laboratory Medicine, 
      Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: 
      jan99966@gmail.com.
FAU - Chou, Teh-Ying
AU  - Chou TY
AD  - Division of Molecular Pathology, Department of Pathology and Laboratory Medicine, 
      Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, 
      School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic 
      address: tychou@vghtpe.gov.tw.
LA  - eng
PT  - Journal Article
DEP - 20160908
PL  - Ireland
TA  - Lung Cancer
JT  - Lung cancer (Amsterdam, Netherlands)
JID - 8800805
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (ROS1 protein, human)
SB  - IM
MH  - Adenocarcinoma/*genetics/*pathology
MH  - Adenocarcinoma of Lung
MH  - Aged
MH  - Algorithms
MH  - ErbB Receptors/genetics
MH  - Female
MH  - Gene Rearrangement
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Lung Neoplasms/*genetics/*pathology
MH  - Male
MH  - Middle Aged
MH  - Mutation
MH  - Neoplasm Staging
MH  - Prospective Studies
MH  - Protein-Tyrosine Kinases/genetics
MH  - Proto-Oncogene Proteins/genetics
OTO - NOTNLM
OT  - Driver mutations
OT  - Immunohistochemistry
OT  - Lung adenocarcinoma
OT  - Molecular testing
EDAT- 2016/10/31 06:00
MHDA- 2017/10/31 06:00
CRDT- 2016/10/31 06:00
PHST- 2016/07/06 00:00 [received]
PHST- 2016/09/06 00:00 [revised]
PHST- 2016/09/07 00:00 [accepted]
PHST- 2016/10/31 06:00 [pubmed]
PHST- 2017/10/31 06:00 [medline]
PHST- 2016/10/31 06:00 [entrez]
AID - S0169-5002(16)30473-1 [pii]
AID - 10.1016/j.lungcan.2016.09.007 [doi]
PST - ppublish
SO  - Lung Cancer. 2016 Nov;101:40-47. doi: 10.1016/j.lungcan.2016.09.007. Epub 2016 
      Sep 8.