PMID- 23625156
OWN - NLM
STAT- MEDLINE
DCOM- 20140123
LR  - 20220330
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 8
IP  - 7
DP  - 2013 Jul
TI  - Detection of ALK rearrangement by immunohistochemistry in lung adenocarcinoma and 
      the identification of a novel EML4-ALK variant.
PG  - 883-91
LID - 10.1097/JTO.0b013e3182904e22 [doi]
AB  - INTRODUCTION: The echinoderm microtubule-associated protein-like 4 anaplastic 
      lymphoma kinase (EML4-ALK) fusion gene has been identified as a potent oncogenic 
      driver in non-small-cell lung cancer, in particular adenocarcinoma (ADC). It 
      defines a unique subgroup of lung ADC, which may be responsive to ALK inhibitors. 
      Detection of ALK rearrangement by fluorescence in situ hybridization (FISH) or 
      reverse transcriptase polymerase chain reaction (RT-PCR) is considered to be the 
      standard procedure, but each with its own limitation. We evaluated the practical 
      usefulness of immunohistochemistry (IHC) to detect ALK expression as a reliable 
      detection method of ALK rearrangement in lung ADC. METHODS: We tested 373 lung 
      ADCs for ALK rearrangement by IHC and FISH. Multiplex RT-PCR was performed to 
      confirm the fusion variants. RESULTS: Twenty-two of 373 lung ACs (5.9%) were 
      positive for ALK immunoreactivity. ALK-positive tumor cells demonstrated strong 
      and diffused granular staining in the cytoplasm. All the ALK IHC-positive cases 
      were confirmed to harbor ALK rearrangement, either by FISH, or RT-PCR. Two cases 
      with positive ALK protein expression, but negative for breakapart FISH signal 
      were shown to harbor EML4-ALK variant 1 by RT-PCR. None of the ALK IHC-negative 
      cases were FISH-positive. In addition, we identified a novel EML4-ALK fusion 
      variant (E3:ins53A20), and its potent transformation potential has been confirmed 
      by in vivo tumorigenicity assay. CONCLUSION: IHC can effectively detect ALK 
      rearrangement in lung cancer. It might provide a reliable and cost-effective 
      diagnostic approach in routine pathologic laboratories for the identification of 
      suitable candidates for ALK-targeted therapy.
FAU - To, Ka-Fai
AU  - To KF
AD  - Department of Anatomical and Cellular Pathology, the Chinese University of Hong 
      Kong, Shatin, Hong Kong. kfto@cuhk.edu.hk
FAU - Tong, Joanna H M
AU  - Tong JH
FAU - Yeung, King S F
AU  - Yeung KS
FAU - Lung, Raymond W M
AU  - Lung RW
FAU - Law, Peggy P Y
AU  - Law PP
FAU - Chau, Shuk Ling
AU  - Chau SL
FAU - Kang, Wei
AU  - Kang W
FAU - Tong, Carol Y K
AU  - Tong CY
FAU - Chow, Chit
AU  - Chow C
FAU - Chan, Anthony W H
AU  - Chan AW
FAU - Leung, Linda K S
AU  - Leung LK
FAU - Mok, Tony S K
AU  - Mok TS
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Thorac Oncol
JT  - Journal of thoracic oncology : official publication of the International 
      Association for the Study of Lung Cancer
JID - 101274235
RN  - 0 (EML4-ALK fusion protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.10.1 (ALK protein, human)
RN  - EC 2.7.10.1 (Alk protein, mouse)
RN  - EC 2.7.10.1 (Anaplastic Lymphoma Kinase)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
MH  - Adenocarcinoma/diagnosis/*genetics
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anaplastic Lymphoma Kinase
MH  - Animals
MH  - Carcinoma, Non-Small-Cell Lung/diagnosis/*genetics
MH  - Cell Transformation, Neoplastic
MH  - Cohort Studies
MH  - Female
MH  - Follow-Up Studies
MH  - *Gene Rearrangement
MH  - Genetic Variation
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/diagnosis/*genetics
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Middle Aged
MH  - NIH 3T3 Cells
MH  - Neoplasm Grading
MH  - Neoplasm Staging
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Prognosis
MH  - RNA, Messenger/genetics
MH  - Receptor Protein-Tyrosine Kinases/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
EDAT- 2013/04/30 06:00
MHDA- 2014/01/24 06:00
CRDT- 2013/04/30 06:00
PHST- 2013/04/30 06:00 [entrez]
PHST- 2013/04/30 06:00 [pubmed]
PHST- 2014/01/24 06:00 [medline]
AID - S1556-0864(15)32871-9 [pii]
AID - 10.1097/JTO.0b013e3182904e22 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2013 Jul;8(7):883-91. doi: 10.1097/JTO.0b013e3182904e22.