title: ALK immunohistochemistry for ALK gene rearrangement screening in non-small cell lung cancer: a systematic review and meta-analysis.
abstract: BACKGROUND
  The aim of this study was to investigate the diagnostic accuracy of anaplastic lymphoma kinase (ALK) immunohistochemistry (IHC) for ALK gene rearrangement in non-small cell lung cancer (NSCLC) through systematic review, meta-analysis and diagnostic test accuracy review.
  
  
  METHODS
  The current study included 11,806 NSCLC cases in 42 eligible studies. We performed concordance analyses between ALK IHC and fluorescence in situ hybridization (FISH). The diagnostic accuracy of ALK IHC was analyzed based on ALK IHC criteria and antibodies.
  
  
  RESULTS
  The overall ALK IHC results were positive in 13.2%. The overall concordance rate between ALK IHC and FISH was 0.950 (95% confidence interval [CI], 0.927-0.966). In the ALK IHC-positive and negative groups, the concordance rates were 0.805 (95% CI 0.733-0.861) and 0.985 (95% CI 0.978-0.990), respectively. The ALK FISH-positive rates were 0.009 (95% CI 0.004-0.023), 0.378 (95% CI 0.217-0.572), 0.628 (95% CI 0.420-0.796) and 0.900 (95% CI 0.840-0.939) in the ALK IHC 0, 1+, 2+ and 3+ groups, respectively. In diagnostic test accuracy review for ALK IHC, the pooled sensitivity and specificity were 0.92 (95% CI 0.89-0.94) and 0.91 (95% CI 0.90-0.91), respectively. The diagnostic odds ratio and the area under the curve on the summary receiver operating characteristic curve were 266.56 (95% CI 110.83-641.14) and 0.983, respectively.
  
  
  CONCLUSIONS
  Our results suggested that ALK IHC equivocal (score 1+ and 2+) cases should not be considered as IHC-negative in screening for ALK gene rearrangement. Additional detailed criteria for ALK IHC equivocal cases are necessary to determine how to best apply this approach in daily practice.
authors.affiliation: Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul - Republic of Korea.|Department of Pathology, Eulji University Hospital, Daejeon, Republic of Korea.
authors.forename: Jung-Soo
authors.initials: JS
authors.lastname: Pyo
authors.affiliation: Department of Pathology, Inje University Sanggye Paik Hospital, Seoul - Republic of Korea.
authors.forename: Guhyun
authors.initials: G
authors.lastname: Kang
authors.affiliation: Department of Pathology, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul - Republic of Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Sohn
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D055088:Early Detection of Cancer; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases