Document Detail

Immunohistochemistry is a reliable screening tool for identification of ALK rearrangement in non-small-cell lung carcinoma and is antibody dependent.
MedLine Citation:
PMID:  23196275     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Fluorescence in situ hybridization (FISH) is the standard procedure for the detection of anaplastic lymphoma receptor tyrosine kinase (ALK) rearrangement in non-small-cell lung carcinoma (NSCLC) but is expensive and time consuming. We tested three antibodies to ALK, using various detection systems, and hypothesized that ALK immunohistochemistry (IHC) may represent a cost-effective and efficient means of screening for ALK rearrangement in NSCLC.
METHODS: We screened 377 stage I or II NSCLC cases in a tissue microarray by FISH and IHC (5A4 [Leica Biosystems Newcastle Ltd, Newcastle upon Tyne, UYnited Kingdom] by Nichirei's N-Histofine ALK detection kit [Nichirei Biosciences inc., Tokyo, Japan], 5A4 by Novocastra with ADVANCE [Dako Canada inc., Burlington, Ontario, Canada], D5F3 by Cell Signaling Technology with ADVANCE [Cell Signalling Technologies inc., Danvers, MA], and DAKO clone ALK1 with FLEX [Dako Canada inc., Burlington, Ontario, Canada] and ADVANCE). IHC was scored as 0, 1+, 2+, or 3+. Possibly positive or positive cases were further analyzed by IHC and FISH on whole section.
RESULTS: Tissue microarray results were available on 377 cases by IHC and 273 cases by FISH. Eleven cases were positive or possibly positive by either IHC or FISH, and three cases were positive or possibly positive by both methods. Three cases were ALK-positive by FISH on whole section validation. There was no correlation between semiquantitative IHC score (1+, 2+, 3+) and ALK rearrangement by FISH. D5F3 (Cell Signaling by ADVANCE) and 5A4 (Novocastra by ADVANCE) showed the greatest combination of sensitivity (100%) and specificity (87.5% for 5A4 by Novocastra and 75% for D5F3 by Cell Signaling), and produced no false-negative results.
CONCLUSIONS: IHC is a reliable screening tool for identification of ALK rearrangement in NSCLC and is antibody dependent. D5F3 (Cell Signaling) and 5A4 (Novocastra) can be used with FISH for identification of IHC-positive cases to reduce screening costs.
Chris M J Conklin; Kenneth J Craddock; Cherry Have; Janessa Laskin; Christian Couture; Diana N Ionescu
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer     Volume:  8     ISSN:  1556-1380     ISO Abbreviation:  J Thorac Oncol     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-17     Completed Date:  2013-06-06     Revised Date:  2013-08-09    
Medline Journal Info:
Nlm Unique ID:  101274235     Medline TA:  J Thorac Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  45-51     Citation Subset:  IM    
University of British Columbia, Vancouver, British Columbia, Canada.
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MeSH Terms
Adenocarcinoma / genetics
Antibodies / diagnostic use*
Carcinoma, Large Cell / genetics
Carcinoma, Non-Small-Cell Lung / genetics*
Carcinoma, Squamous Cell / genetics
Cost-Benefit Analysis
False Negative Reactions
False Positive Reactions
Gene Rearrangement
Immunohistochemistry* / economics
In Situ Hybridization, Fluorescence
Lung Neoplasms / genetics*
Middle Aged
Receptor Protein-Tyrosine Kinases / genetics*,  immunology*
Sensitivity and Specificity
Tissue Array Analysis
Reg. No./Substance:
0/Antibodies; EC Protein-Tyrosine Kinases; EC lymphoma kinase
Comment In:
J Thorac Oncol. 2013 Jul;8(7):e67-8   [PMID:  23774392 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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