title: EGFR, FLT1 and heparanase as markers identifying patients at risk of short survival in cholangiocarcinoma.
abstract: BACKGROUND
  Cholangiocarcinoma remains to be a tumor with very few treatment choices and limited prognosis. In this study, we sought to determine the prognostic role of fms-related tyrosine kinase 1/vascular endothelial growth factor receptor 1 (FLT1/VEGFR1), heparanase (HPSE) and epidermal growth factor receptor (EGFR) gene expression in patients with resected CCC.
  
  
  METHODS
  47 formalin-fixed paraffin embedded FFPE tumor samples from patients with resected CCC were analyzed. FFPE tissues were dissected using laser-captured microdissection and analyzed for FLT1, FLT4, HPSE, Hif1a, VEGFA/C, HB-EGF, PDGFA, PDGF-RA and EGFR mRNA expression using a quantitative real-time RT-PCR method. Gene expression values (relative mRNA levels) are expressed as ratios between the target gene and internal reference genes (beta-actin, b2mg, rplp2, sdha).
  
  
  RESULTS
  EGFR, FLT1 and HPSE expression levels were significantly associated with overall survival (OS). FLT1 showed the strongest significant independent association with overall survival in a multivariate cox regression analysis when compared to the other genes and clinicopathological factors with a nearly 5 times higher relative risk (4.74) of dying earlier when expressed in low levels (p = 0.04). ROC Curve Analysis revealed that measuring EGFR potentially identifies patients at risk of a worsened outcome with a sensitivity of 80% and a specificity of 75% (p = 0.01).
  
  
  CONCLUSIONS
  EGFR and FLT1 seem to be potential markers to identify those patients at high risk of dying from cholangiocarcinoma. Therefore these markers may help to identify patient subgroups in need for a more aggressive approach in a disease that is in desperate need for new approaches.
authors.affiliation: Department of Medical Oncology, West German Cancer Center, University Duisburg-Essen, Essen, Germany. ach@o117.com
authors.forename: Andreas-Claudius
authors.initials: AC
authors.lastname: Hoffmann
authors.forename: Eray
authors.initials: E
authors.lastname: Goekkurt
authors.forename: Peter V
authors.initials: PV
authors.lastname: Danenberg
authors.forename: Sylvia
authors.initials: S
authors.lastname: Lehmann
authors.forename: Gerhard
authors.initials: G
authors.lastname: Ehninger
authors.forename: Daniela E
authors.initials: DE
authors.lastname: Aust
authors.forename: Jan
authors.initials: J
authors.lastname: Stoehlmacher-Williams
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000201:enzymology / Q000473:pathology*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D018281:Cholangiocarcinoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D012307:Risk Factors; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism*; D000099175:Heparanase
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D005966:Glucuronidase; D040281:Vascular Endothelial Growth Factor Receptor-1; D000099175:Heparanase; C512478:EGFR protein, human; C501162:FLT1 protein, human