PMID- 27562706
OWN - NLM
STAT- MEDLINE
DCOM- 20170215
LR  - 20190221
IS  - 1432-2307 (Electronic)
IS  - 0945-6317 (Linking)
VI  - 469
IP  - 5
DP  - 2016 Nov
TI  - ALK+ lung adenocarcinoma in never smokers and long-term ex-smokers: prevalence 
      and detection by immunohistochemistry and fluorescence in situ hybridization.
PG  - 533-540
AB  - ALK gene rearrangements are identified in 2-5 % of all non-small cell lung cancer 
      and are more common in lifetime non-smokers with adenocarcinoma, but the 
      prevalence of ALK rearrangements is not as well characterized in long-term 
      ex-smokers (quit >10 years prior to diagnosis). Accurate and timely diagnosis of 
      ALK-rearranged tumors is of clinical importance given the remarkable response to 
      targeted inhibitors. ALK gene rearrangement may be detected by fluorescence in 
      situ hybridization (FISH), and abnormal expression of ALK protein may be detected 
      by immunohistochemistry (IHC), the latter of which is faster and less expensive. 
      The aim of this study is to evaluate the prevalence of ALK rearrangement in 
      non-smokers and long-term ex-smokers with lung adenocarcinoma and to assess the 
      performance of IHC for the detection of ALK+ tumors when compared to FISH. Two 
      hundred fifty-one cases of resected lung adenocarcinoma were retrospectively 
      reviewed, including non-smokers (n = 79) or long-term ex-smokers (n = 172). ALK 
      IHC and ALK FISH were performed on each case. Four cases demonstrated ALK 
      rearrangement by FISH (4/251; 1.6 %). All cases were non-smokers (4/79; 5.1 %), 
      and all were positive for ALK by IHC. No additional cases were considered 
      positive by IHC, and only 26 (10.4 %) cases were considered equivocal using a 
      conservative approach to interpretation, resulting in a sensitivity of 100 % and 
      specificity of 89.5 %. ALK rearrangement was not observed in lung adenocarcinoma 
      arising in long-term ex-smokers, whereas it is seen in up to 5.1 % of lifetime 
      non-smokers. ALK IHC using the 5A4 antibody demonstrates high sensitivity, 
      supporting its use as a screening test.
FAU - Williams, Andrew S
AU  - Williams AS
AD  - Department of Pathology, Dalhousie University and Queen Elizabeth II Health 
      Sciences Centre, Halifax, NS, Canada.
FAU - Greer, Wenda
AU  - Greer W
AD  - Department of Pathology, Dalhousie University and Queen Elizabeth II Health 
      Sciences Centre, Halifax, NS, Canada.
FAU - Bethune, Drew
AU  - Bethune D
AD  - Department of Surgery, Dalhousie University and Queen Elizabeth II Health 
      Sciences Centre, Halifax, NS, Canada.
FAU - Craddock, Kenneth J
AU  - Craddock KJ
AD  - Department of Pathology, University Health Network, Toronto, ON, Canada.
FAU - Flowerdew, Gordon
AU  - Flowerdew G
AD  - Department of Community Health and Epidemiology, Dalhousie University, Halifax, 
      NS, Canada.
FAU - Xu, Zhaolin
AU  - Xu Z
AD  - Department of Pathology, Dalhousie University and Queen Elizabeth II Health 
      Sciences Centre, Halifax, NS, Canada. zxu3@dal.ca.
AD  - Division of Anatomical Pathology, Queen Elizabeth II Health Sciences Centre, 5788 
      University Ave. Rm 734C, Halifax, B3H 1V8, NS, Canada. zxu3@dal.ca.
LA  - eng
PT  - Journal Article
DEP - 20160825
PL  - Germany
TA  - Virchows Arch
JT  - Virchows Archiv : an international journal of pathology
JID - 9423843
RN  - 0 (Oncogene Proteins, Fusion)
RN  - 0 (Smoke)
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
MH  - Adenocarcinoma/diagnosis/*epidemiology/*genetics
MH  - Adenocarcinoma of Lung
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Anaplastic Lymphoma Kinase
MH  - Female
MH  - *Gene Rearrangement
MH  - Humans
MH  - Immunohistochemistry/methods
MH  - In Situ Hybridization, Fluorescence/methods
MH  - Lung Neoplasms/diagnosis/*epidemiology/*genetics
MH  - Male
MH  - Middle Aged
MH  - Oncogene Proteins, Fusion/genetics
MH  - Prevalence
MH  - Receptor Protein-Tyrosine Kinases/*genetics
MH  - Retrospective Studies
MH  - Smoke/adverse effects
OTO - NOTNLM
OT  - 5A4
OT  - Anaplastic lymphoma tyrosine kinase (ALK)
OT  - Ex-smoker
OT  - Fluorescence in situ hybridization (FISH)
OT  - Immunohistochemistry (IHC)
OT  - Lung cancer
OT  - Non-smoker
EDAT- 2016/10/28 06:00
MHDA- 2017/02/16 06:00
CRDT- 2016/08/27 06:00
PHST- 2016/03/04 00:00 [received]
PHST- 2016/08/11 00:00 [accepted]
PHST- 2016/06/14 00:00 [revised]
PHST- 2016/10/28 06:00 [pubmed]
PHST- 2017/02/16 06:00 [medline]
PHST- 2016/08/27 06:00 [entrez]
AID - 10.1007/s00428-016-2005-y [pii]
AID - 10.1007/s00428-016-2005-y [doi]
PST - ppublish
SO  - Virchows Arch. 2016 Nov;469(5):533-540. doi: 10.1007/s00428-016-2005-y. Epub 2016 
      Aug 25.