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Strong coexpression of osteopontin and vascular endothelial growth factor correlates with survival in clear cell renal-cell carcinoma

Osteopontin (OPN) is a highly phosphorylated protein with numerous functions, including roles in bone remodelling, cell-adhesion, cell-mediated immunity, cell signalling, and angiogenesis. It has been recognized as a transformation-associated protein and as a potential prognostic factor for various human cancers. Several lines of experiments have implicated OPN in angiogenesis, and it has been shown that vascular endothelial growth factor may induce expression of OPN. Also, it has been shown that osteopontin overproduced by tumour cells acts as a potent angiogenic factor contributing to tumour growth. The aim of this study was to analyse the relationship between the OPN and vascular endothelial growth factor (VEGF) expression in clear cell renal-cell carcinoma. Also, we have analysed the association of VEGF and OPN coexpression with disease outcome. A total of 81 clear cell renal-cell carcinomas were immunohistochemically analyzed for the OPN and VEGF expression and scored in a semi-quantitative manner, by combining tumour epithelial proportion score and intensity score. Statistical analysis was performed by nonparametric Spearman’s correlation coefficient method. Survival probabilities were estimated by the univariate Kaplan-Meier method and survival curves were compared by the log-rank test. Renal-cell carcinomas showed heterogeneous staining pattern for both OPN and VEGF, ranging from focal expression of low intensity to strong and diffuse cytoplasmic staining of tumor cells. We found statistically significant correlation between OPN and VEGF expression at the level p=0.0026, (rs=0.3304). Also, the survival of patients with strong OPN and VEGF coexpression was significantly worse compared to those with either low or without OPN and VEGF coexpression (p<0.003). Our results show the upregulation of OPN and VEGF in clear cell renal-cell carcinomas. The correlation between their expression and the association of their strong coexpression with poor disease outcome support the hypothesis that cooperation of OPN and VEGF may facilitate tumor progression in human cancer.

adenocarcinoma; carcinoma; renal cell; osteopontin; VEGF; survival; immunohistochemistry

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