title: Clinicopathologic implication of ALK rearrangement in surgically resected lung cancer: a proposal of diagnostic algorithm for ALK-rearranged adenocarcinoma.
abstract: BACKGROUND
  To characterize the clinicopathologic features of ALK-rearranged lung cancer, and suggest a molecular test protocol for lung adenocarcinoma in the small biopsy specimen.
  
  
  METHODS
  In 735 NSCLC surgical specimens, clinicopathologic features, ALK protein over-expression by immunohistochemistry (IHC), and ALK rearrangement by fluorescence in situ hybridization (FISH) as well as EGFR and KRAS mutation studies were analyzed.
  
  
  RESULTS
  Of the 735 NSCLC cases, 28 (3.8%) were ALK FISH-positive. ALK rearrangement, EGFR and KRAS mutation were mutually exclusive. ALK rearrangement was significantly higher in adenocarcinomas (6.8%, p<0.001), younger age (p<0.0007), women (7.6%, p<0.001), and never-smokers (8.9%, p<0.001) with no gender difference in the adenocarcinoma or never-smoker subgroup. ALK FISH-positivity was not associated with disease recurrence (HR, 0.79; 95% CI, 0.42-1.49) or overall survival (HR, 0.61; 95% CI, 0.24-1.55). However, ALK-rearranged lung cancer tended to show more frequent lymph node metastasis despite its lower T stage. Similar to EGFR-mutated lung cancer, ALK-rearranged lung cancer was enriched in adenocarcinoma, women, and never-smokers. The results of ALK IHC and FISH obtained from tissue microarray (TMA)/biopsy specimens and whole sections after resection were concordant.
  
  
  CONCLUSIONS
  ALK rearrangement was not a significant prognostic factor in surgically resectable NSCLC. The clinical profiles of ALK-rearranged lung cancer patients overlapped with those of EGFR-mutated patients. Therefore, we suggest that simultaneous tests for ALK IHC and EGFR mutation (Chung's SNUBH molecular test protocol), which has important implications for the storage and use of small biopsy or cytology samples for genetic analysis.
authors: Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Republic of Korea.
authors: Jin Ho
authors: JH
authors: Paik
authors: Chang-Min
authors: CM
authors: Choi
authors: Hyojin
authors: H
authors: Kim
authors: Se Jin
authors: SJ
authors: Jang
authors: Gheeyoung
authors: G
authors: Choe
authors: Dong Kwan
authors: DK
authors: Kim
authors: Hwa Jung
authors: HJ
authors: Kim
authors: Hoil
authors: H
authors: Yoon
authors: Choon-Taek
authors: CT
authors: Lee
authors: Sanghoon
authors: S
authors: Jheon
authors: Ji-Young
authors: JY
authors: Choe
authors: Jin-Haeng
authors: JH
authors: Chung
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000077548:Anaplastic Lymphoma Kinase; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality / Q000601:surgery; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012307:Risk Factors; D016019:Survival Analysis; D014178:Translocation, Genetic; D055815:Young Adult
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases