title: Amplification but not translocation of anaplastic lymphoma kinase is a frequent event in oesophageal cancer.
abstract: BACKGROUND
  Translocations of anaplastic lymphoma kinase (ALK) to various fusions partners and formation of oncogenic fusions proteins have been demonstrated in a variety of human malignancies. These fusion-proteins are potential pharmaceutically targets. Aim of this study was to investigate ALK gene status in a large cohort of squamous cell carcinoma (SCC) and adenocarcinoma (AC) of the oesophagus.
  
  
  METHODS
  117 SCCs and 136 ACs were included into this study. ALK and EML4 gene status were evaluated by fluorescence in situ hybridisation (FISH) using a triple colour break apart single fusion probe and a probe against 2p11. ALK and EML4 protein expression was determined by immunohistochemistry. Data on expression of ALK downstream effector tyrosine-705 phosphorylated STAT3 (pSTAT3) were available from a previous study.
  
  
  RESULTS
  FISH was performed successfully in 251 cases. All cases were negative for ALK translocations, while 14/135 (12.1%) of SCCs and 14/116 (10.4%) of ACs showed ALK amplifications. Concomitant EML4 amplifications were present in 27/28 cases with ALK amplifications. Three cases (two SCC, one with additional ALK &EML4 amplification and one AC) showed EML4 translocations not involving ALK. None of the tumours with ALK amplification showed ALK protein expression, and no correlation with clinical parameters, survival or pSTAT3 expression was observed.
  
  
  CONCLUSIONS
  While ALK translocations are not present in oesophageal cancer, ALK amplifications are common events with comparable rates in SCC and AC. Since ALK amplified breast cancer cells were shown to respond to ALK inhibitors, ALK amplified oesophageal cancers might be considered as possible candidates for therapies targeting ALK.
authors.affiliation: Department of Surgery, Upper GI Research Unit, Medical University of Vienna, Austria. sebastian.schoppmann@meduniwien.ac.at
authors.forename: Sebastian F
authors.initials: SF
authors.lastname: Schoppmann
authors.forename: Berthold
authors.initials: B
authors.lastname: Streubel
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000077548:Anaplastic Lymphoma Kinase; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005784:Gene Amplification; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D014178:Translocation, Genetic
chemical_list: D018797:Cell Cycle Proteins; D008869:Microtubule-Associated Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; C415585:EML4 protein, human; D012697:Serine Endopeptidases