title: Brain metastases of gastro-oesophageal cancer: evaluation of molecules with relevance for targeted therapies.
abstract: BACKGROUND
  Brain metastases (BM) of gastro-oesophageal cancer are exceedingly rare and only limited data exist on their pathobiology.
  
  
  METHODS
  We identified tissue samples of BM of gastro-oesophageal cancer and analyzed the expression of human epidermal growth factor receptor-2 (HER2), phosphorylated signal transducer and activator of transcription-3 (pSTAT3), epithelial growth factor receptor (EGFR), V600E point mutation of the v-raf murine sarcoma viral oncogene homolog-B1 (BRAF V600E), cluster of differentiation molecule-34 (CD34), hypoxia inducible factor-1α (HIF 1-α) and Ki-67 by immunohistochemical methods.
  
  
  RESULTS
  Our series comprised of twenty adenocarcinomas and one oesophageal squamous cell carcinoma. Three (14%), 7 (33%), 9 (43%), 18 (86%) and 0 BM specimens were scored positively for HER2, EGFR, pSTAT3, HIF1-α and BRAF V600E expression. The median Ki-67 index was 59%. The microvascular density was moderate-to-high and active intratumoral microvascular sprouting was evident in 20/21 (95%) of BMs. The HER2 and EGFR expression status were consistent between primary tumors and BM in all three assessable cases. HIF1-α and pSTAT3 expression were significantly higher in HER2-positive cases.
  
  
  CONCLUSIONS
  Therapeutic use of agents targeting HER2, pSTAT3, EGFR and angiogenesis may be feasible for selected BM of gastro-esophageal cancer. HER2 positivity does not seem to predispose to brain colonization in gastro-esophageal cancer.
authors.affiliation: Medical University of Vienna, Department of Surgery, Waehringer Guertel 18-20, 1090 Vienna, Austria. sebastian.schoppmann@meduniwien.ac.at
authors.forename: Matthias
authors.initials: M
authors.lastname: Preusser
authors.forename: Anna S
authors.initials: AS
authors.lastname: Berghoff
authors.forename: Aysegül
authors.initials: A
authors.lastname: Ilhan-Mutlu
authors.forename: Carina
authors.initials: C
authors.lastname: Dinhof
authors.forename: Manuel
authors.initials: M
authors.lastname: Magerle
authors.forename: Christine
authors.initials: C
authors.lastname: Marosi
authors.forename: Michael
authors.initials: M
authors.lastname: Hejna
authors.forename: David
authors.initials: D
authors.lastname: Capper
authors.forename: Andreas
authors.initials: A
authors.lastname: VON Deimling
authors.forename: Sebastian F
authors.initials: SF
authors.lastname: Schoppmann
authors.forename: Peter
authors.initials: P
authors.lastname: Birner
mesh_terms: D000368:Aged; D001932:Brain Neoplasms / Q000556:secondary*; D066246:ErbB Receptors / Q000032:analysis; D004938:Esophageal Neoplasms / Q000737:chemistry / Q000473:pathology*; D004943:Esophagogastric Junction; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000032:analysis; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009154:Mutation; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis; D050796:STAT3 Transcription Factor / Q000502:physiology; D013274:Stomach Neoplasms / Q000737:chemistry / Q000473:pathology*
chemical_list: D066246:ErbB Receptors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D048493:Proto-Oncogene Proteins B-raf; D018719:Erb-b2 Receptor Tyrosine Kinases; D050796:STAT3 Transcription Factor; C497442:HIF1A protein, human; C494086:STAT3 protein, human; C508053:ERBB2 protein, human; C482119:BRAF protein, human