title: VEGFR2 predicts decreased patients survival in soft tissue sarcomas.
abstract: OBJECTIVE
  Tyrosine kinases are promising targets for personalized medicine, and new drugs are currently in phase 2 and phase 3 clinical trials. However, expression analysis of tyrosine kinases as predictive biomarkers is still not a standard approach. Furthermore, only limited studies have investigated the expression of tyrosine kinase receptors on the protein level. In this study, we analysed a well-characterised group of soft tissue sarcomas for different tyrosine kinase receptors and correlated the results with clinicopathological parameters, including survival.
  
  
  METHODS
  275 soft tissue sarcomas of our Sarcoma center at the Ludwig-Maximilians-University (LMU) were reinvestigated and categorized according to the current WHO classification system. The tumor collective included undifferentiated pleomorphic sarcomas (n=81), leiomyosarcomas (n=50), synovial sarcomas (n=27), liposarcomas (n=51), angiosarcomas (n=43) and other soft tissue sarcomas (n=23).
  
  
  RESULTS
  On protein levels, high expression of VEGFR1 was detected immunohistochemically in 61%, VEGFR2 (KDR) in 11%, VEGFR3 in 64%, PDGFRA in 42% and PDGFRB in 73%. High expression of VEGFR1-3 and PDGFRB was significantly correlated with higher grading (G2 vs G3, p<0.05), and high VEGFR2 was significantly correlated with decreased patients' survival (p<0.001).
  
  
  CONCLUSIONS
  Tyrosine kinase receptors showed a distinct expression pattern in soft tissue sarcomas. High expression of VEGFR2 (KDR) is significantly associated with decreased patients' survival. High VEGFR 1-3 and PDGFRB are significantly correlated with higher tumor grading. Protein signatures might be evaluated before targeted therapy to give a rationale for an eligible personalized therapy.
authors: Department of Internal Medicine III, Ludwig-Maximilians-University (LMU), Munich, Germany.
authors: Eric
authors: E
authors: Kampmann
authors: Department of General, Visceral und Vascular Surgery, Friedrich-Schiller University, Jena, Germany.
authors: Annelore
authors: A
authors: Altendorf-Hofmann
authors: Department of Internal Medicine III, Ludwig-Maximilians-University (LMU), Munich, Germany.
authors: Sebastian
authors: S
authors: Gibis
authors: Department of Internal Medicine III, Ludwig-Maximilians-University (LMU), Munich, Germany.
authors: Lars H
authors: LH
authors: Lindner
authors: Department of Internal Medicine III, Ludwig-Maximilians-University (LMU), Munich, Germany.
authors: Rolf
authors: R
authors: Issels
authors: Institute of Pathology, Ludwig-Maximilians-University (LMU), Munich, Germany.
authors: Thomas
authors: T
authors: Kirchner
authors: Institute of Pathology, Ludwig-Maximilians-University (LMU), Munich, Germany. Electronic address: Thomas.Knoesel@med.uni-muenchen.de.
authors: Thomas
authors: T
authors: Knösel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012509:Sarcoma / Q000175:diagnosis* / Q000378:metabolism* / Q000401:mortality; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*; D055815:Young Adult
chemical_list: C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Immunohistochemistry; PDGFR; Sarcoma; Survival; VEGFR