title: A novel, highly sensitive ALK antibody 1A4 facilitates effective screening for ALK rearrangements in lung adenocarcinomas by standard immunohistochemistry.
abstract: BACKGROUND
  Successful treatment of lung cancer patients with crizotinib depends on the accurate diagnosis of anaplastic lymphoma receptor tyrosine kinase (ALK) gene rearrangements. The approved fluorescence in-situ hybridization test is complex and difficult to use in daily diagnostic practice. Immunohistochemical assays-rapid and perfectly adapted for routine pathology practice-have been proposed as alternatives. We evaluated the novel high affinity ALK 1A4 antibody for routine diagnostics in formalin fixed, paraffin-embedded tumor specimens.
  
  
  METHODS
  Detection of ALK protein expression was investigated by comparing the new 1A4 antibody and the established D5F3 antibody/Ventana system in 218 lung cancer specimens with known ALK status preanalyzed by quantitative reverse transcription-polymerase chain reaction and fluorescence in-situ hybridization (20 ALK-positive cases, 198 ALK-negative cases).
  
  
  RESULTS
  The accuracy of both immunohistochemical assays for the detection of ALK rearrangements was high. Using a conventional staining procedure without signal enhancement, the 1A4 antibody assay identified all 20 ALK-rearranged tumors (100% sensitivity) and correctly characterized 196 of 198 negative cases (99.1% specificity). The D5F3/Ventana assay detected 19 ALK-rearranged tumors and typed 217 of 218 tumors correctly (95% sensitivity, 99.5 % specificity).
  
  
  CONCLUSIONS
  The novel 1A4 antibody represents a promising candidate for screening lung tumors for the presence of ALK rearrangements.
authors: *Department of Clinical Pathology, Robert-Bosch-Krankenhaus and Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; and ‡Center for Pulmonology and Thoracic Surgery, Klinik Schillerhöhe, Gerlingen, Stuttgart, Germany.
authors: Kim
authors: K
authors: Gruber
authors: Martin
authors: M
authors: Kohlhäufl
authors: Godehard
authors: G
authors: Friedel
authors: German
authors: G
authors: Ott
authors: Claudia
authors: C
authors: Kalla
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D000077192:Adenocarcinoma of Lung; D000077548:Anaplastic Lymphoma Kinase; D000912:Antibodies, Neoplasm / Q000276:immunology*; D004273:DNA, Neoplasm / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000912:Antibodies, Neoplasm; D004273:DNA, Neoplasm; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases