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.

Muckenhuber, Alexander; Babitzki, Galina; Thomas, Marlene; Hölzlwimmer, Gabriele; Zajac, Magdalena; Jesinghaus, Moritz; Bergmann, Frank; Werner, Jens; Stenzinger, Albrecht; Weichert, Wilko

doi:10.1097/MPA.0000000000000604

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journal article

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.
Document type:: Journal Article; Article
Author(s):: Muckenhuber, Alexander; Babitzki, Galina; Thomas, Marlene; Hölzlwimmer, Gabriele; Zajac, Magdalena; Jesinghaus, Moritz; Bergmann, Frank; Werner, Jens; Stenzinger, Albrecht; Weichert, Wilko
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 ? = 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 ? = 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.
Journal title abbreviation:: Pancreas
Year:: 2016
Journal volume:: 45
Journal issue:: 8
Pages contribution:: 1167-74
Language:: eng
Fulltext / DOI:: doi:10.1097/MPA.0000000000000604
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/26825865
Print-ISSN:: 0885-3177
TUM Institution:: Institut für Allgemeine Pathologie und Pathologische Anatomie
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mediaTUM Gesamtbestand Hochschulbibliographie 2016 Fakultäten Medizin Institut für Allgemeine Pathologie und Pathologische Anatomie

mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Preclinical Medicine Institut für Allgemeine Pathologie und Pathologische Anatomie (Dr. Mogler komm.)2016