title: Unique clinicopathologic features characterize ALK-rearranged lung adenocarcinoma in the western population.
abstract: OBJECTIVE
  The anaplastic large cell kinase gene (ALK) is rearranged in approximately 5% of lung adenocarcinomas within the Asian population. We evaluated the incidence and the characteristics of ALK-rearranged lung adenocarcinomas within the western population and the optimal diagnostic modality to detect ALK rearrangements in routine clinical practice.
  
  
  METHODS
  We tested 358 lung adenocarcinomas from three institutions for ALK rearrangements by fluorescent in situ hybridization (FISH) and immunohistochemistry with and without tyramide amplification. The clinicopathologic characteristics of tumors with and without ALK rearrangements were compared.
  
  
  RESULTS
  We identified 20 (5.6%) lung adenocarcinomas with ALK rearrangements within our cohort of western patients. ALK rearrangement was associated with younger age (P = 0.0002), never smoking (P < 0.0001), advanced clinical stage (P = 0.0001), and a solid histology with signet-ring cells (P < 0.0001). ALK rearrangement was identified by FISH in 95% of cases and immunohistochemistry with and without tyramide amplification in 80% and 40% of cases, respectively, but neither FISH nor immunohistochemistry alone detected all cases with ALK rearrangement on initial screening. None of the ALK-rearranged tumors harbored coexisting EGFR mutations.
  
  
  CONCLUSIONS
  Lung adenocarcinomas with ALK rearrangements are uncommon in the western population and represent a distinct entity of carcinomas with unique characteristics. For suspected cases, dual diagnostic testing, with FISH and immunohistochemistry, should be considered to accurately identify lung adenocarcinomas with ALK rearrangement.
authors: Department of Pathology, Brigham & Women's Hospital, Boston, Massachusetts 02115, USA.
authors: Scott J
authors: SJ
authors: Rodig
authors: Mari
authors: M
authors: Mino-Kenudson
authors: Sanja
authors: S
authors: Dacic
authors: Beow Y
authors: BY
authors: Yeap
authors: Alice
authors: A
authors: Shaw
authors: Justine A
authors: JA
authors: Barletta
authors: Hannah
authors: H
authors: Stubbs
authors: Kenny
authors: K
authors: Law
authors: Neal
authors: N
authors: Lindeman
authors: Eugene
authors: E
authors: Mark
authors: Pasi A
authors: PA
authors: Janne
authors: Thomas
authors: T
authors: Lynch
authors: Bruce E
authors: BE
authors: Johnson
authors: A John
authors: AJ
authors: Iafrate
authors: Lucian R
authors: LR
authors: Chirieac
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D020732:Cytogenetic Analysis; D004252:DNA Mutational Analysis; D005260:Female; D005828:Genetics, Population; D018095:Germ-Line Mutation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D019366:Western World
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases