Open AccessFluorescence In Situ Hybridization, Immunohistochemistry, and Next‐Generation Sequencing for Detection of EML4‐ALK Rearrangement in Lung Cancer
Author(s) -
PekarZlotin Marina,
Hirsch Fred R.,
SoussanGutman Lior,
Ilouze Maya,
Dvir Addie,
Boyle Theresa,
Wynes Murry,
Miller Vincent A.,
Lipson Doron,
Palmer Gary A.,
Ali Siraj M.,
Dekel Shlomi,
Brenner Ronen,
Bunn Paul A.,
Peled Nir
Publication year - 2015
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2014-0389
Subject(s) - crizotinib , immunohistochemistry , fluorescence in situ hybridization , medicine , lung cancer , fish <actinopterygii> , adenocarcinoma , in situ hybridization , oncology , cancer , pathology , cancer research , biology , gene , gene expression , genetics , fishery , malignant pleural effusion , chromosome
Background. The U.S. Food and Drug Administration‐approved method for detecting EML4‐ALK rearrangement is fluorescence in situ hybridization (FISH); however, data supporting the use of immunohistochemistry (IHC) for that purpose are accumulating. Previous studies that compared FISH and IHC considered FISH the gold standard, but none compared data with the results of next‐generation sequencing (NGS) analysis. Materials and Methods. We studied FISH and IHC (D5F3 antibody) systematically for EML4‐ALK rearrangement in 51 lung adenocarcinoma patients, followed by NGS in case of discordance. Results. Of 51 patients, 4 were positive with FISH (7.8%), and 8 were positive with IHC (15.7%). Three were positive with both. NGS confirmed that four of the five patients who were positive with IHC and negative with FISH were positive for ALK. Two were treated by crizotinib, with progression‐free survival of 18 and 6 months. Considering NGS as the most accurate test, the sensitivity and specificity were 42.9% and 97.7%, respectively, for FISH and 100% and 97.7%, respectively, for IHC. Conclusion. The FISH‐based method of detecting EML4‐ALK rearrangement in lung cancer may miss a significant number of patients who could benefit from targeted ALK therapy. Screening for EML4‐ALK rearrangement by IHC should be strongly considered, and NGS is recommended in borderline cases. Two patients who were negative with FISH and positive with IHC were treated with crizotinib and responded to therapy.