PMID- 25721120
OWN - NLM
STAT- MEDLINE
DCOM- 20150713
LR  - 20220318
IS  - 1549-490X (Electronic)
IS  - 1083-7159 (Print)
IS  - 1083-7159 (Linking)
VI  - 20
IP  - 3
DP  - 2015 Mar
TI  - Fluorescence in situ hybridization, immunohistochemistry, and next-generation 
      sequencing for detection of EML4-ALK rearrangement in lung cancer.
PG  - 316-22
LID - 10.1634/theoncologist.2014-0389 [doi]
AB  - 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.
CI  - (c)AlphaMed Press.
FAU - Pekar-Zlotin, Marina
AU  - Pekar-Zlotin M
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel.
FAU - Hirsch, Fred R
AU  - Hirsch FR
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel.
FAU - Soussan-Gutman, Lior
AU  - Soussan-Gutman L
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel.
FAU - Ilouze, Maya
AU  - Ilouze M
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel.
FAU - Dvir, Addie
AU  - Dvir A
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel.
FAU - Boyle, Theresa
AU  - Boyle T
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel.
FAU - Wynes, Murry
AU  - Wynes M
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel.
FAU - Miller, Vincent A
AU  - Miller VA
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel.
FAU - Lipson, Doron
AU  - Lipson D
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel.
FAU - Palmer, Gary A
AU  - Palmer GA
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel.
FAU - Ali, Siraj M
AU  - Ali SM
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel.
FAU - Dekel, Shlomi
AU  - Dekel S
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel.
FAU - Brenner, Ronen
AU  - Brenner R
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel.
FAU - Bunn, Paul A Jr
AU  - Bunn PA Jr
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel.
FAU - Peled, Nir
AU  - Peled N
AD  - Thoracic Cancer Research and Detection Center, Sheba Medical Center, Ramat Gan, 
      Israel; Tel Aviv University, Tel Aviv, Israel; University of Colorado Cancer 
      Center, Division of Medical Oncology, University of Colorado, Aurora, Colorado, 
      USA; Oncotest, Teva Pharmaceutical Industries Ltd., Petah Tikva, Israel; Thoracic 
      Cancer Unit, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel; 
      Foundation Medicine, Cambridge, Massachusetts, USA; The Institute of Oncology, 
      Wolfson Medical Center, Holon, Israel nirp@post.tau.ac.il.
LA  - eng
GR  - P30 CA046934/CA/NCI NIH HHS/United States
GR  - P50 CA058187/CA/NCI NIH HHS/United States
PT  - Comparative Study
PT  - Journal Article
DEP - 20150226
PL  - England
TA  - Oncologist
JT  - The oncologist
JID - 9607837
RN  - 0 (EML4-ALK fusion protein, human)
RN  - 0 (Oncogene Proteins, Fusion)
SB  - IM
CIN - Oncologist. 2015 Aug;20(8):e24. PMID: 26156326
CIN - Oncologist. 2015 Aug;20(8):e25. PMID: 26156328
MH  - Adenocarcinoma/*genetics/*metabolism/pathology
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Algorithms
MH  - Cross-Sectional Studies
MH  - Disease Progression
MH  - Female
MH  - *Gene Rearrangement
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Lung Neoplasms/*genetics/*metabolism/pathology
MH  - Male
MH  - Mass Screening/*methods
MH  - Middle Aged
MH  - Oncogene Proteins, Fusion/*genetics
MH  - Retrospective Studies
MH  - Sensitivity and Specificity
MH  - Survival Rate
PMC - PMC4350802
OTO - NOTNLM
OT  - EML4-ALK
OT  - Fluorescence in situ hybridization
OT  - Immunohistochemistry
OT  - Next-generation sequencing
OT  - Non-small cell lung cancer
COIS- Disclosures of potential conflicts of interest may be found at the end of this 
      article.
EDAT- 2015/02/28 06:00
MHDA- 2015/07/15 06:00
PMCR- 2016/03/01
CRDT- 2015/02/28 06:00
PHST- 2015/02/28 06:00 [entrez]
PHST- 2015/02/28 06:00 [pubmed]
PHST- 2015/07/15 06:00 [medline]
PHST- 2016/03/01 00:00 [pmc-release]
AID - theoncologist.2014-0389 [pii]
AID - T14389 [pii]
AID - 10.1634/theoncologist.2014-0389 [doi]
PST - ppublish
SO  - Oncologist. 2015 Mar;20(3):316-22. doi: 10.1634/theoncologist.2014-0389. Epub 
      2015 Feb 26.