title: ALK+ lung adenocarcinoma in never smokers and long-term ex-smokers: prevalence and detection by immunohistochemistry and fluorescence in situ hybridization.
abstract: 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.
authors: Department of Pathology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada.
authors: Andrew S
authors: AS
authors: Williams
authors: Department of Pathology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada.
authors: Wenda
authors: W
authors: Greer
authors: Department of Surgery, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada.
authors: Drew
authors: D
authors: Bethune
authors: Department of Pathology, University Health Network, Toronto, ON, Canada.
authors: Kenneth J
authors: KJ
authors: Craddock
authors: Department of Community Health and Epidemiology, Dalhousie University, Halifax, NS, Canada.
authors: Gordon
authors: G
authors: Flowerdew
authors: Department of Pathology, Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada. zxu3@dal.ca.|Division of Anatomical Pathology, Queen Elizabeth II Health Sciences Centre, 5788 University Ave. Rm 734C, Halifax, B3H 1V8, NS, Canada. zxu3@dal.ca.
authors: Zhaolin
authors: Z
authors: Xu
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D008175:Lung Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D015995:Prevalence; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D012906:Smoke / Q000009:adverse effects
chemical_list: D015514:Oncogene Proteins, Fusion; D012906:Smoke; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases
keywords: 5A4; Anaplastic lymphoma tyrosine kinase (ALK); Ex-smoker; Fluorescence in situ hybridization (FISH); Immunohistochemistry (IHC); Lung cancer; Non-smoker