title: Co-expression of receptor tyrosine kinases in esophageal adenocarcinoma and squamous cell cancer.
abstract: This study aimed to define the co-expression pattern of target receptor tyrosine kinases (RTKs) in human esophageal adenocarcinoma and squamous cell cancer. The co-expression pattern of vascular endothelial growth factor receptor (VEGFR)1-3, platelet-derived growth factor receptor (PDGFR)alpha/beta and epidermal growth factor receptor 1 (EGFR1) was analyzed by RT-PCR in 50 human esophageal cancers (35 adenocarcinomas and 15 squamous cell cancers). In addition, IHC staining was applied for the confirmation of the expression and analysis of RTK localisation. The adenocarcinoma samples revealed VEGFR1 (97%), VEGFR2 (94%), VEGFR3 (77%), PDGFRalpha (91%), PDGFRbeta (85%) and EGFR1 (97%) expression at different intensities. Ninety-four percent of the esophageal adenocarcinomas expressed at least four out of six RTKs. Similarly, squamous cell cancers revealed VEGFR1 (100%), VEGFR2 (100%), VEGFR3 (53%), PDGFRalpha (100%), PDGFRbeta (87%) and EGFR1 (100%) expression at different intensities. All esophageal squamous cell carcinomas expressed at least four out of six RTKs. While VEGFR1-3 and PDGFRalpha and EGFR1 was expressed by tumor cells, PDGFRbeta was restricted to stromal cells, which also depicted a PDGFRalpha expression. Our results revealed a high rate of RTK co-expression in esophageal adenocarcinoma and squamous cell cancer and may encourage application of multi-target RTK inhibitors within a multimodal concept as a promising novel approach for innovative treatment strategies.
authors.affiliation: Department of General and Abdominal Surgery, Johannes Gutenberg University of Mainz, Mainz, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Gockel
authors.forename: Markus
authors.initials: M
authors.lastname: Moehler
authors.forename: Kirsten
authors.initials: K
authors.lastname: Frerichs
authors.forename: Daniel
authors.initials: D
authors.lastname: Drescher
authors.forename: Tran Tong
authors.initials: TT
authors.lastname: Trinh
authors.forename: Friedrich
authors.initials: F
authors.lastname: Duenschede
authors.forename: Thomas
authors.initials: T
authors.lastname: Borschitz
authors.forename: Katrin
authors.initials: K
authors.lastname: Schimanski
authors.forename: Stefan
authors.initials: S
authors.lastname: Biesterfeld
authors.forename: Kerstin
authors.initials: K
authors.lastname: Herzer
authors.forename: Peter R
authors.initials: PR
authors.lastname: Galle
authors.forename: Hauke
authors.initials: H
authors.lastname: Lang
authors.forename: Theodor
authors.initials: T
authors.lastname: Junginger
authors.forename: Carl C
authors.initials: CC
authors.lastname: Schimanski
mesh_terms: D000230:Adenocarcinoma / Q000201:enzymology*; D002294:Carcinoma, Squamous Cell / Q000201:enzymology*; D066246:ErbB Receptors / Q000032:analysis; D004938:Esophageal Neoplasms / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D020794:Receptor Protein-Tyrosine Kinases / Q000032:analysis*; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000032:analysis; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000032:analysis; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000032:analysis; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000032:analysis
chemical_list: D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D040321:Vascular Endothelial Growth Factor Receptor-3