Document Detail

Combined use of ALK immunohistochemistry and FISH for optimal detection of ALK-rearranged lung adenocarcinomas.
MedLine Citation:
PMID:  23407557     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: ALK gene rearrangements occur in approximately 5% of lung adenocarcinomas (ACAs), leading to anaplastic lymphoma kinase (ALK) overexpression and predicting response to targeted therapy. Fluorescence in situ hybridization (FISH) is the standard procedure for detection of ALK rearrangements in lung ACA but requires specialized equipment and expertise. Immunohistochemistry (IHC) for ALK protein overexpression is a promising screening modality, with reports of newer antibodies showing excellent sensitivity and specificity for ALK-rearranged lung ACA.
METHODS: In this study, we analyzed ALK IHC (5A4 clone) in 186 cases from our clinical service and compared it with ALK FISH and EGFR and KRAS mutation status.
RESULTS: Twelve cases had concordant ALK protein overexpression and ALK rearrangement by FISH. Three ALK-rearranged cases lacked ALK protein expression. Of these discrepant cases, one had a coexisting EGFR mutation and a subtle atypical ALK rearrangement manifested as a break in the 5' centromeric portion of the FISH probe. One case had a concurrent BRAF mutation. Follow-up testing on a metastasis revealed absence of the ALK rearrangement, with persistent BRAF mutation. In one ALK-rearranged protein negative case, very limited tissue remained for ALK IHC, raising the possibility of false negativity because of protein expression heterogeneity. Importantly, ALK protein expression was detected in one case initially thought not to have an ALK rearrangement. In this case, FISH was falsely negative because of interference by benign reactive nuclei. After correcting for these cases, ALK IHC was 93% sensitive and 100% specific as compared with FISH.
CONCLUSIONS: ALK IHC improves the detection of ALK rearrangements when used together with FISH, and its use in lung ACA genetic testing algorithms should be considered.
Lynette M Sholl; Stanislawa Weremowicz; Stacy W Gray; Kwok-Kin Wong; Lucian R Chirieac; Neal I Lindeman; Jason L Hornick
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Publication Detail:
Type:  Case Reports; Journal Article    
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 Mar 
Date Detail:
Created Date:  2013-02-14     Completed Date:  2013-07-30     Revised Date:  2014-03-06    
Medline Journal Info:
Nlm Unique ID:  101274235     Medline TA:  J Thorac Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  322-8     Citation Subset:  IM    
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MeSH Terms
Adenocarcinoma / diagnosis*,  genetics,  metabolism
Follow-Up Studies
Gene Rearrangement*
Genetic Testing
Immunoenzyme Techniques
In Situ Hybridization, Fluorescence*
Lung Neoplasms / diagnosis*,  genetics,  metabolism
Middle Aged
Mutation / genetics
Neoplasm Staging
Proto-Oncogene Proteins / genetics
Receptor Protein-Tyrosine Kinases / genetics*,  metabolism*
Receptor, Epidermal Growth Factor / genetics
Sensitivity and Specificity
Survival Rate
Tumor Markers, Biological / genetics
ras Proteins / genetics
Grant Support
Reg. No./Substance:
0/KRAS protein, human; 0/Proto-Oncogene Proteins; 0/Tumor Markers, Biological; EC protein, human; EC Protein-Tyrosine Kinases; EC, Epidermal Growth Factor; EC lymphoma kinase; EC Proteins
Comment In:
J Thorac Oncol. 2014 Feb;9(2):e18-9   [PMID:  24419430 ]
J Thorac Oncol. 2013 Mar;8(3):255-6   [PMID:  23407554 ]

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

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