title: Accurate identification of ALK positive lung carcinoma patients: novel FDA-cleared automated fluorescence in situ hybridization scanning system and ultrasensitive immunohistochemistry.
abstract: BACKGROUND
  Based on the excellent results of the clinical trials with ALK-inhibitors, the importance of accurately identifying ALK positive lung cancer has never been greater. However, there are increasing number of recent publications addressing discordances between FISH and IHC. The controversy is further fuelled by the different regulatory approvals. This situation prompted us to investigate two ALK IHC antibodies (using a novel ultrasensitive detection-amplification kit) and an automated ALK FISH scanning system (FDA-cleared) in a series of non-small cell lung cancer tumor samples.
  
  
  METHODS
  Forty-seven ALK FISH-positive and 56 ALK FISH-negative NSCLC samples were studied. All specimens were screened for ALK expression by two IHC antibodies (clone 5A4 from Novocastra and clone D5F3 from Ventana) and for ALK rearrangement by FISH (Vysis ALK FISH break-apart kit), which was automatically captured and scored by using Bioview's automated scanning system.
  
  
  RESULTS
  All positive cases with the IHC antibodies were FISH-positive. There was only one IHC-negative case with both antibodies which showed a FISH-positive result. The overall sensitivity and specificity of the IHC in comparison with FISH were 98% and 100%, respectively.
  
  
  CONCLUSIONS
  The specificity of these ultrasensitive IHC assays may obviate the need for FISH confirmation in positive IHC cases. However, the likelihood of false negative IHC results strengthens the case for FISH testing, at least in some situations.
authors.affiliation: Laboratorio de Dianas Terapéuticas, Centro Integral Oncológico "Clara Campal", Hospital Universitario Madrid Sanchinarro, Universidad San Pablo-CEU, Madrid, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Conde
authors.affiliation: Laboratorio de Dianas Terapéuticas, Centro Integral Oncológico "Clara Campal", Hospital Universitario Madrid Sanchinarro, Universidad San Pablo-CEU, Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Suárez-Gauthier
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Amparo
authors.initials: A
authors.lastname: Benito
authors.affiliation: Hospital Ramón y Cajal, Madrid, Spain.
authors.forename: Pilar
authors.initials: P
authors.lastname: Garrido
authors.affiliation: C.H.U. A Coruña, La Coruña, Spain.
authors.forename: Rosario
authors.initials: R
authors.lastname: García-Campelo
authors.affiliation: Hospital Virgen del Rocío, Sevilla, Spain.
authors.forename: Michele
authors.initials: M
authors.lastname: Biscuola
authors.affiliation: Hospital Virgen del Rocío, Sevilla, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.affiliation: IdiPAZ (Hospital La Paz Institute for Health Research), University Hospital La Paz, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Hardisson
authors.affiliation: IdiPAZ (Hospital La Paz Institute for Health Research), University Hospital La Paz, Faculty of Medicine, Autonomous University of Madrid, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: de Castro
authors.affiliation: Hospital Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Camacho
authors.affiliation: Hospital Insular de Gran Canaria, Las Palmas de Gran Canaria, Spain.
authors.forename: Delvys
authors.initials: D
authors.lastname: Rodriguez-Abreu
authors.affiliation: C.H.U. Santiago de Compostela, Santiago de Compostela, Spain.
authors.forename: Ihab
authors.initials: I
authors.lastname: Abdulkader
authors.affiliation: Hospital Clinic, Barcelona, Spain.
authors.forename: Josep
authors.initials: J
authors.lastname: Ramirez
authors.affiliation: Hospital Clinic, Barcelona, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Reguart
authors.affiliation: Hospital del Mar-Parc de Salut Mar, Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Salido
authors.affiliation: Hospital del Mar-Parc de Salut Mar, Barcelona, Spain.
authors.forename: Lara
authors.initials: L
authors.lastname: Pijuán
authors.affiliation: Hospital del Mar-Parc de Salut Mar, Barcelona, Spain.
authors.forename: Edurne
authors.initials: E
authors.lastname: Arriola
authors.affiliation: Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Julián
authors.initials: J
authors.lastname: Sanz
authors.affiliation: Hospital Central de Asturias, Oviedo, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Folgueras
authors.affiliation: Hospital Central de Asturias, Oviedo, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Villanueva
authors.affiliation: Hospital Marqués de Valdecilla, Santander, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Gómez-Román
authors.affiliation: Oncology Department, Centro Integral Oncológico "Clara Campal", Hospital Universitario Madrid Sanchinarro, Universidad San Pablo-CEU, Madrid, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Hidalgo
authors.affiliation: Laboratorio de Dianas Terapéuticas, Centro Integral Oncológico "Clara Campal", Hospital Universitario Madrid Sanchinarro, Universidad San Pablo-CEU, Madrid, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: López-Ríos
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D000906:Antibodies; D057205:Automation, Laboratory; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis* / Q000235:genetics; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008175:Lung Neoplasms / Q000175:diagnosis* / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis* / Q000235:genetics*; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000906:Antibodies; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases