title: Vascular endothelial growth factor receptor 2, but not S100A4 or S100A6, correlates with prolonged survival in advanced urothelial carcinoma.
abstract: OBJECTIVE
  A major challenge in muscle-invasive urothelial carcinoma (UC) is to identify biomarkers that can predict disease prognosis and treatment response after cystectomy. Therefore, we analyzed the potential prognostic value of the proteins vascular endothelial growth factor receptor 2 (VEGFR2), S100A4, and S100A6 in UC.
  
  
  METHODS
  Retrospective outcome data and tumor specimens from 83 cystectomy patients with histologically confirmed invasive UC were included. Expression levels of VEGFR2 (also called flk-1 and KDR), S100A4, and S100A6 were analyzed in primary tumor tissue by immunohistochemistry.
  
  
  RESULTS
  Immunohistochemical staining and analysis of VEGFR2, S100A4, and S100A6 showed localization mainly in tumor cell cytoplasm. High VEGFR2 expression and low tumor category were independent variables associated with longer overall survival (OS) and disease-free survival, revealed by a bivariate Cox proportional hazards regression model (both P<0.001). In addition, the univariate log-rank test and the Cox model demonstrated that OS beyond 2 years was significantly greater among patients with low S100A6 expression than in those with high S100A6 expression (P = 0.017 and 0.022, respectively). Differences in tumor expression of S100A4 were not significantly associated with outcome.
  
  
  CONCLUSIONS
  In this study, VEGFR2 expression was significantly correlated with risk of disease relapse and OS in a defined cohort of patients with UC of the bladder treated by cystectomy.
authors.affiliation: Department of Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden. Electronic address: carl-henrik.shah@karolinska.se.
authors.forename: Carl-Henrik
authors.initials: CH
authors.lastname: Shah
authors.affiliation: Department of Oncology-Pathology, Karolinska Biomics Center, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Kristina
authors.initials: K
authors.lastname: Viktorsson
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lena
authors.initials: L
authors.lastname: Kanter
authors.affiliation: Urology and Andrology, Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.
authors.forename: Amir
authors.initials: A
authors.lastname: Sherif
authors.affiliation: Department of Pathology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Jurate
authors.initials: J
authors.lastname: Asmundsson
authors.affiliation: Department of Urology, Södersjukhuset, Stockholm, Sweden.
authors.forename: Robert
authors.initials: R
authors.lastname: Rosenblatt
authors.affiliation: Department of Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Rolf
authors.initials: R
authors.lastname: Lewensohn
authors.affiliation: Department of Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden; Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Ullén
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D000075383:S100 Calcium Binding Protein A6; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism*; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000473:pathology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D000075383:S100 Calcium Binding Protein A6; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C055351:S100A6 protein, human; C077591:S100A4 protein, human; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Advanced urothelial carcinoma; S100A4; S100A6; VEGFR2