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.

CONCLUSION:

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: Carl-Henrik Shah, Kristina Viktorsson, Lena Kanter, Amir Sherif, Jurate Asmundsson, Robert Rosenblatt, Rolf Lewensohn, Anders Ullén
• Journal: Urologic oncology (Urol Oncol) Vol. 32 Issue 8 Pg. 1215-24 (Nov 2014) ISSN: 1873-2496 [Electronic] United States
• PMID: 24880461 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Cell Cycle Proteins
• S100 Calcium Binding Protein A6
• S100 Calcium-Binding Protein A4
• S100 Proteins
• S100A6 protein, human
• S100A4 protein, human
• KDR protein, human
• Vascular Endothelial Growth Factor Receptor-2

Topics

• Aged
• Biomarkers, Tumor (metabolism)
• Cell Cycle Proteins (metabolism)
• Disease-Free Survival
• Female
• Humans
• Immunohistochemistry
• Male
• Middle Aged
• Prognosis
• Retrospective Studies
• S100 Calcium Binding Protein A6
• S100 Calcium-Binding Protein A4
• S100 Proteins (metabolism)
• Survival Analysis
• Urinary Bladder Neoplasms (metabolism, pathology)
• Vascular Endothelial Growth Factor Receptor-2 (metabolism)