title: Rare ALK expression but no ALK rearrangement in pancreatic ductal adenocarcinoma and neuroendocrine tumors.
abstract: OBJECTIVE
  Anaplastic lymphoma kinase (ALK) gene rearrangements were first identified in anaplastic large cell lymphomas. Subsequently, they have been observed in other tumor types with ALK-rearranged tumors demonstrating responsiveness to ALK inhibitors. The aggressiveness of pancreatic ductal adenocarcinoma warrants the examination of ALK rearrangements in pancreatic cancer as a potential therapeutic target. Immunohistochemical expression of ALK1 correlates with ALK rearrangements in other tumors. We performed ALK immunohistochemistry on samples of pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors using 2 tissue microarrays.
  
  
  METHODS
  ALK1 expression was scored for each case as 0, 1+, 2+, or 3+ using established criteria. Fluorescence in situ hybridization using a break-apart assay with probes for ALK was performed to detect ALK rearrangement in ALK1-positive cases.
  
  
  RESULTS
  All 46 neuroendocrine tumors were negative for ALK1. Of 140 ductal adenocarcinoma cases, 5 showed immunoreactivity for ALK1: 1 was 3+, 2 were 2+, and 2 were 1+. However, fluorescence in situ hybridization for ALK rearrangement was negative in all 5 cases.
  
  
  CONCLUSIONS
  The results demonstrate that ALK1 expression is uncommon in both pancreatic ductal adenocarcinoma and neuroendocrine tumors. Rare ALK1 expression is not induced by ALK translocation, and ALK is unlikely to be a therapeutic target in pancreatic tumors.
authors.affiliation: Division of Anatomic Pathology, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: Rondell P D
authors.initials: RP
authors.lastname: Graham
authors.forename: Andre M
authors.initials: AM
authors.lastname: Oliveira
authors.forename: Lizhi
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology* / Q000235:genetics; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D021441:Carcinoma, Pancreatic Ductal / Q000201:enzymology* / Q000235:genetics; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018358:Neuroendocrine Tumors / Q000201:enzymology* / Q000235:genetics; D010179:Pancreas / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis* / Q000235:genetics; D046888:Tissue Array Analysis
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases