title: Profiling of cMET and HER Family Receptor Expression in Pancreatic Ductal Adenocarcinomas and Corresponding Lymph Node Metastasis to Assess Relevant Pathways for Targeted Therapies: Looking at the Soil Before Planting the Seed.
abstract: Comprehensive assessment of cMET and HER family receptor tyrosine kinases expression, changes of expression during metastatic progression, amplification status of the MET gene, and correlations with patient characteristics in pancreatic ductal adenocarcinoma (PDAC) was conducted.
  
  
  
  We investigated 56 PDACs and corresponding lymph node metastases for HER1 to HER4 and cMET expression by immunohistochemistry, as well as cMET gene copy numbers by chromogenic in situ hybridization.
  
  
  
  Of all receptor tyrosine kinases evaluated, cMET expression was highest with 46.5% of tumors showing moderate or strong expression and a weak correlation with gene copy number status (P = 0.04; Spearman ρ = 0.28). cMET expression was increased in metastases. In contrast, expression levels of HER family receptors were generally low both in primaries and metastases. A weak yet significant correlation of HER1 and cMET expression levels was observed (P < 0.001; Spearman ρ = 0.44) and HER1 was often present in poorly differentiated tumors (G3, P = 0.049).
  
  
  
  Our data suggest that cMET might constitute an interesting molecule for combining targeted and chemotherapeutic approaches in PDAC, because expression is frequent and increased during metastatic progression. In PDAC, cMET protein expression might be a more useful stratification biomarker than cMET gene amplification, which does not seem to be its primary regulator.
authors.affiliation: From the *Institute of Pathology, University Hospital Heidelberg, Ruprecht-Karls Universität, Heidelberg; †Roche Pharma Research and Early Development, Roche Innovation Center, Penzberg, Germany; ‡AstraZeneca, Personalized Healthcare and Biomarkers, Innovative Medicines and Early Development, Cambridge, United Kingdom; §Department of Surgery, University Hospital Grosshadern, Ludwig-Maximilians-Universität, München, Germany; ∥National Center for Tumor Diseases, Heidelberg; and ¶German Cancer Consortium (DKTK), Dresden, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Muckenhuber
authors.forename: Galina
authors.initials: G
authors.lastname: Babitzki
authors.forename: Marlene
authors.initials: M
authors.lastname: Thomas
authors.forename: Gabriele
authors.initials: G
authors.lastname: Hölzlwimmer
authors.forename: Magdalena
authors.initials: M
authors.lastname: Zajac
authors.forename: Moritz
authors.initials: M
authors.lastname: Jesinghaus
authors.forename: Frank
authors.initials: F
authors.lastname: Bergmann
authors.forename: Jens
authors.initials: J
authors.lastname: Werner
authors.forename: Albrecht
authors.initials: A
authors.lastname: Stenzinger
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
mesh_terms: D021441:Carcinoma, Pancreatic Ductal; D066246:ErbB Receptors; D005260:Female; D006801:Humans; D008198:Lymph Nodes; D008207:Lymphatic Metastasis; D019859:Proto-Oncogene Proteins c-met
chemical_list: D066246:ErbB Receptors; C491743:MET protein, human; D019859:Proto-Oncogene Proteins c-met