title: Correlation of IHC and FISH for ALK gene rearrangement in non-small cell lung carcinoma: IHC score algorithm for FISH.
abstract: BACKGROUND
  Accurate, cost-effective methods for testing anaplastic lymphoma kinase gene rearrangement (ALK+) are needed to select patients with non-small cell lung carcinoma for ALK-inhibitor therapy. Fluorescent in situ hybridization (FISH) is used to detect ALK+, but it is expensive and not routinely available. We explored the potential of an immunohistochemistry (IHC) scoring system as an affordable, accessible approach.
  
  
  METHODS
  One hundred one samples were obtained from an enriched cohort of never-smokers with adenocarcinoma from the Mayo Clinic Lung Cancer Cohort. IHC was performed using the ALK1 monoclonal antibody with ADVANCE detection system (Dako) and FISH with dual-color, break-apart probe (Abbott Molecular) on formalin-fixed, paraffin-embedded tissue.
  
  
  RESULTS
  Cases were assessed as IHC score 0 (no staining; n = 69), 1+ (faint cytoplasmic staining, n = 21), 2+ (moderate, smooth cytoplasmic staining; n = 3), or 3+ (intense, granular cytoplasmic staining in ≥10% of tumor cells; n = 8). All IHC 3+ cases were FISH+, whereas 1 of 3 IHC 2+ and 1 of 21 IHC 1+ cases were FISH+. All 69 IHC 0 cases were FISH-. Considering FISH a gold-standard reference in this study, sensitivity and specificity of IHC were 90 and 97.8%, respectively, when 2+ and 3+ were regarded as IHC positive and 0 and 1+ as IHC negative.
  
  
  CONCLUSIONS
  IHC scoring correlates with FISH and may be a useful algorithm in testing ALK+ by FISH in non-small cell lung carcinoma, similar to human epidermal growth factor-2 testing in breast cancer. Further study is needed to validate this approach.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA. yi.joanne@mayo.edu
authors.forename: Eunhee S
authors.initials: ES
authors.lastname: Yi
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Boland
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Maleszewski
authors.forename: Anja C
authors.initials: AC
authors.lastname: Roden
authors.forename: Andre M
authors.initials: AM
authors.lastname: Oliveira
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Aubry
authors.forename: Michele R
authors.initials: MR
authors.lastname: Erickson-Johnson
authors.forename: Bolette L
authors.initials: BL
authors.lastname: Caron
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Tang
authors.forename: Shawn
authors.initials: S
authors.lastname: Stoddard
authors.forename: Jason
authors.initials: J
authors.lastname: Wampfler
authors.forename: Kimary
authors.initials: K
authors.lastname: Kulig
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000465:Algorithms; D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D012680:Sensitivity and Specificity
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases