PMID- 27418132
OWN - NLM
STAT- MEDLINE
DCOM- 20180206
LR  - 20220410
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 7
IP  - 39
DP  - 2016 Sep 27
TI  - Responses to crizotinib in patients with ALK-positive lung adenocarcinoma who 
      tested immunohistochemistry (IHC)-positive and fluorescence in situ hybridization 
      (FISH)-negative.
PG  - 64410-64420
LID - 10.18632/oncotarget.10560 [doi]
AB  - Although the Ventana immunohistochemistry (IHC) platform for detecting anaplastic 
      lymphoma kinase gene (ALK) (D5F3) expression was recently approved by the US Food 
      and Drugs Administration (FDA), fluorescence in situ hybridization (FISH) is 
      still the "gold-standard" method recommended by the US National Comprehensive 
      Cancer Network (NCCN) guideline for NSCLC. We evaluated 6 ALK-positive lung 
      adenocarcinoma patients who tested Ventana IHC-positive and FISH-negative and 
      assessed their clinical responses to the ALK tyrosine kinase inhibitor (TKI) 
      crizotinib. Histologic and cytologic specimens from the 6 patients were stained 
      with Ventana anti-ALK(D5F3) rabbit monoclonal primary antibody using the 
      OptiView DAB IHC detection kit and OptiView amplification kit on a Ventana 
      BenchMark XT processor. In addition, they were also tested by FISH, qRT-PCR, 
      next-generation sequencing (NGS), and RNAscope ISH analysis. All patients 
      received crizotinib treatment and their follow-up clinical data were recorded. 
      The objective response rate achieved with crizotinib therapy was 66.7% (4/6 
      partial responses and 2/6 stable disease). One patient in whom a new fusion type 
      (EML4->EXOC6B->ALK fusion) was identified obtained a partial response. These 
      findings indicate that patients with ALK-positive lung adenocarcinoma who test 
      Ventana IHC-positive and FISH-negative may still respond to crizotinib therapy.
FAU - Ma, Di
AU  - Ma D
AD  - Department of Medical Oncology, Cancer Institute & Hospital, Chinese Academy of 
      Medical Sciences, Beijing, China.
FAU - Wang, Zheng
AU  - Wang Z
AD  - Department of Pathology, Beijing Hospital of the Ministry of Health, Beijing, 
      China.
FAU - Yang, Lin
AU  - Yang L
AD  - Department of Pathology, Cancer Institute & Hospital, Chinese Academy of Medical 
      Sciences, Beijing, China.
FAU - Mu, Xinlin
AU  - Mu X
AD  - Department of Respiratory and Critical Care Medicine, Peking University People's 
      Hospital, Beijing, China.
FAU - Wang, Yan
AU  - Wang Y
AD  - Department of Medical Oncology, Cancer Institute & Hospital, Chinese Academy of 
      Medical Sciences, Beijing, China.
FAU - Zhao, Xinming
AU  - Zhao X
AD  - Department of Diagnostic Radiology, Cancer Institute & Hospital, Chinese Academy 
      of Medical Sciences, Beijing, China.
FAU - Li, Junling
AU  - Li J
AD  - Department of Medical Oncology, Cancer Institute & Hospital, Chinese Academy of 
      Medical Sciences, Beijing, China.
FAU - Lin, Dongmei
AU  - Lin D
AD  - Key Laboratory of Carcinogenesis and Translational Research (Ministry of 
      Education), Department of Pathology, Peking University Cancer Hospital & 
      Institute, Beijing, China.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (EML4-ALK fusion protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Pyrazoles)
RN  - 0 (Pyridines)
RN  - 53AH36668S (Crizotinib)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Adenocarcinoma/*drug therapy/enzymology/genetics/pathology
MH  - Adenocarcinoma of Lung
MH  - Adult
MH  - Aged
MH  - Anaplastic Lymphoma Kinase
MH  - Antineoplastic Agents/adverse effects/*therapeutic use
MH  - Biomarkers, Tumor/*antagonists & inhibitors/genetics
MH  - China
MH  - Crizotinib
MH  - Female
MH  - Humans
MH  - *Immunohistochemistry
MH  - *In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/*drug therapy/enzymology/genetics/pathology
MH  - Male
MH  - Middle Aged
MH  - Oncogene Proteins, Fusion/genetics
MH  - Patient Selection
MH  - Precision Medicine
MH  - Predictive Value of Tests
MH  - Protein Kinase Inhibitors/adverse effects/*therapeutic use
MH  - Pyrazoles/adverse effects/*therapeutic use
MH  - Pyridines/adverse effects/*therapeutic use
MH  - Receptor Protein-Tyrosine Kinases/*antagonists & inhibitors/genetics
MH  - Time Factors
MH  - Tomography, X-Ray Computed
MH  - Treatment Outcome
PMC - PMC5325453
OTO - NOTNLM
OT  - ALK status
OT  - crizotinib
OT  - fluorescence in situ hybridization
OT  - immunohistochemistry
OT  - non-small-cell lung cancer
COIS- CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.
EDAT- 2016/07/16 06:00
MHDA- 2018/02/07 06:00
PMCR- 2016/09/27
CRDT- 2016/07/16 06:00
PHST- 2015/09/21 00:00 [received]
PHST- 2016/06/29 00:00 [accepted]
PHST- 2016/07/16 06:00 [pubmed]
PHST- 2018/02/07 06:00 [medline]
PHST- 2016/07/16 06:00 [entrez]
PHST- 2016/09/27 00:00 [pmc-release]
AID - 10560 [pii]
AID - 10.18632/oncotarget.10560 [doi]
PST - ppublish
SO  - Oncotarget. 2016 Sep 27;7(39):64410-64420. doi: 10.18632/oncotarget.10560.