PMID- 21258247
OWN - NLM
STAT- MEDLINE
DCOM- 20110621
LR  - 20220316
IS  - 1556-1380 (Electronic)
IS  - 1556-0864 (Linking)
VI  - 6
IP  - 3
DP  - 2011 Mar
TI  - Screening of anaplastic lymphoma kinase rearrangement by immunohistochemistry in 
      non-small cell lung cancer: correlation with fluorescence in situ hybridization.
PG  - 466-72
LID - 10.1097/JTO.0b013e31820b82e8 [doi]
AB  - BACKGROUND: The use of a standard immunohistochemistry (IHC) assay to detect the 
      anaplastic lymphoma kinase (ALK) protein in lung cancer is challenging. There are 
      no universally accepted, evidence-based guidelines on identifying patients with 
      ALK-rearranged lung cancer using IHC. METHODS: We retrospectively reviewed 465 
      resected specimens of non-small cell lung cancer using a tissue microarray as a 
      test set. ALK protein expression using IHC with 5A4 monoclonal antibody 
      (Novocastra) and ALK gene rearrangement using fluorescence in situ hybridization 
      (FISH) with dual-color break-apart probes (Abbott molecular) were examined. 
      Immunoreactivity was scored as 0, 1, 2, or 3, and the results were compared with 
      the FISH results. A diagnostic algorithm was derived from the correlation of the 
      IHC and FISH results and applied to an additional 187 adenocarcinoma samples used 
      as a validation set. RESULTS: In the test set, ALK protein expression was 
      detected in 40 patients (40/465, 8.6%), consisting of IHC scores of 1 (n = 14), 2 
      (n = 10), and 3 (n = 16), whereas 19 patients (19/453, 4.2%) were FISH-positive. 
      All the FISH-positive patients were assigned IHC scores of 2 or 3. All the 
      patients with ALK IHC scores of 3 were FISH-positive, those with scores of 0 or 1 
      were FISH-negative, and those with scores of 2 were FISH variable. In the 
      validation set, ALK protein expression was detected in 14 patients (scores of 1, 
      n = 2; scores of 2, n = 6; and scores of 3, n = 6), of which nine patients 
      (9/187, 4.8%) were FISH-positive. All the patients with IHC scores of 0 or 1 were 
      FISH-negative, and those with scores of 3 were FISH- positive. Among the patients 
      with IHC scores of 2, three (3/6, 50%) were FISH-positive. CONCLUSIONS: The 
      sensitivity and specificity of IHC was 100% and 95.8%, respectively. These data 
      supported an IHC scoring algorithm in which ALK IHC scores of 0, 1, or 3 were 
      highly compatible with FISH results, and IHC scores of 2 were variable. Based on 
      these findings, the IHC assay using the 5A4 antibody reliably detected non-small 
      cell lung cancer with ALK rearrangement and may be useful as a screening method 
      to identify these tumors.
FAU - Paik, Jin Ho
AU  - Paik JH
AD  - Department of Pathology, Seoul National University Bundang Hospital, Seoul 
      National University College of Medicine, Seongnam, Gyeunggi-do, South Korea.
FAU - Choe, Gheeyoung
AU  - Choe G
FAU - Kim, Hyojin
AU  - Kim H
FAU - Choe, Ji-Young
AU  - Choe JY
FAU - Lee, Hyun Ju
AU  - Lee HJ
FAU - Lee, Choon-Taek
AU  - Lee CT
FAU - Lee, Jong Seok
AU  - Lee JS
FAU - Jheon, Sanghoon
AU  - Jheon S
FAU - Chung, Jin-Haeng
AU  - Chung JH
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
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  - 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
CIN - J Thorac Oncol. 2011 Mar;6(3):411-3. PMID: 21317739
MH  - Adenocarcinoma/diagnosis/genetics/metabolism
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anaplastic Lymphoma Kinase
MH  - Carcinoma, Large Cell/diagnosis/genetics/metabolism
MH  - Carcinoma, Non-Small-Cell Lung/*diagnosis/genetics/metabolism
MH  - Carcinoma, Squamous Cell/diagnosis/genetics/metabolism
MH  - Cohort Studies
MH  - Female
MH  - Follow-Up Studies
MH  - *Gene Rearrangement
MH  - Humans
MH  - Immunoenzyme Techniques
MH  - *In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/*diagnosis/genetics/metabolism
MH  - Male
MH  - Middle Aged
MH  - Neoplasm Staging
MH  - Prognosis
MH  - Receptor Protein-Tyrosine Kinases/*genetics/*metabolism
MH  - Retrospective Studies
MH  - Sensitivity and Specificity
MH  - Tissue Array Analysis
MH  - Young Adult
EDAT- 2011/01/25 06:00
MHDA- 2011/06/22 06:00
CRDT- 2011/01/25 06:00
PHST- 2011/01/25 06:00 [entrez]
PHST- 2011/01/25 06:00 [pubmed]
PHST- 2011/06/22 06:00 [medline]
AID - S1556-0864(15)32199-7 [pii]
AID - 10.1097/JTO.0b013e31820b82e8 [doi]
PST - ppublish
SO  - J Thorac Oncol. 2011 Mar;6(3):466-72. doi: 10.1097/JTO.0b013e31820b82e8.