title: Next-generation sequencing facilitates detection of the classic E13-A20 EML4-ALK fusion in an ALK-FISH/IHC inconclusive biopsy of a stage IV lung cancer patient: a case report.
abstract: BACKGROUND
  Inhibition of the oncogenic fusion-gene EML4-ALK is a current first-line approach for patients with stage IV non-small cell lung cancer. While FISH was established as the gold standard for identifying these patients, there is accumulating evidence that other methods of detection, i.e., immunohistochemistry and next-generation sequencing (NGS), exist that may be equally successful. However, the concordance of these methods is under investigation.
  
  
  METHODS
  Adding to the current literature, we here report a 56 year old female never-smoker with stage IV lung adenocarcinoma whose biopsy was IHC and FISH inconclusive but positive in NGS. Retroactive profiling of the resection specimen corroborated fusion reads obtained by NGS, FISH-positivity and showed weak ALK-positivity by IHC. Consequently, we diagnosed the case as ALK-positive rendering the patient eligible to crizotinib treatment.
  
  
  CONCLUSIONS
  With IHC on biopsy material only, this case would have been overlooked withholding effective therapy.
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
authors.forename: Anna-Lena
authors.initials: AL
authors.lastname: Volckmar
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Endris
authors.affiliation: Thoracic Oncology, Thoraxklinik, University of Heidelberg, and Translational Lung Research Center Heidelberg, 69120, Heidelberg, Germany.|German Center for Lung Research (DZL), Heidelberg, Germany.
authors.forename: Farastuk
authors.initials: F
authors.lastname: Bozorgmehr
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Lier
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
authors.forename: Carlota
authors.initials: C
authors.lastname: Porcel
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Kirchner
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
authors.forename: Jonas
authors.initials: J
authors.lastname: Leichsenring
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Penzel
authors.affiliation: Thoracic Oncology, Thoraxklinik, University of Heidelberg, and Translational Lung Research Center Heidelberg, 69120, Heidelberg, Germany.|German Center for Lung Research (DZL), Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.|German Cancer Consortium (DKTK), Heidelberg, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schirmacher
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany.|Thoracic Oncology, Thoraxklinik, University of Heidelberg, and Translational Lung Research Center Heidelberg, 69120, Heidelberg, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Warth
authors.affiliation: Institute of Pathology, University Hospital Heidelberg, Im Neuenheimer Feld 224, 69120, Heidelberg, Germany. albrecht.stenzinger@med.uni-heidelberg.de.|German Cancer Consortium (DKTK), Heidelberg, Germany. albrecht.stenzinger@med.uni-heidelberg.de.
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stenzinger
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000077192:Adenocarcinoma of Lung; D001706:Biopsy; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D015514:Oncogene Proteins, Fusion / Q000032:analysis*
chemical_list: C522504:EML4-ALK fusion protein, human; D015514:Oncogene Proteins, Fusion
keywords: ALK; EML4-ALK; FISH; NGS; Variant 1; immunohistochemistry