Abstract 5570: Prognostic biomarkers in patients with clear cell renal cell carcinoma (ccRCC)

Abstract

In Argentina the renal cell carcinoma (RCC) is the 9th cause of death for cancer in males and 13th in women. Clear cell RCC (ccRCC), the most common histological type of RCC, exhibits a wide spectrum of molecular characteristics that are closely associated with the deregulations of metabolic pathways involved in oxygen-, iron-, energy-, or nutrient-sensing. Primary ccRCC comprises a heterogeneous group of entities with variable clinical outcomes, so the understanding of their molecular features has critical importance to define individual metastatic risk. The aim of this study was to determine tumor tissue expression of specific molecules associated with angiogenic pathways triggered by hypoxic conditions (VEGFR1/Flk-1, VEGFR2/Flt-4 and PDGF-A receptor), with the glucose metabolism (Glut-1) or with survival pathways (p53). Antigen expressions were analyzed by immunohistochemistry on formalin fixed paraffin embedded ccRRC tumors [men: n=18, age: Md 55 years (range 46-72); women: n=12, age: 54.5 (49-82)], from patients who underwent a surgical resection as first treatment. The relationships between the expression of the different antigens and the known prognostic factors in ccRCC were analyzed by Chi-square. The Pearson test was used for correlation analysis. The Kaplan-Meier method was used to estimate disease-free survival (DFS). We observed that about 60-70% of ccRCC tumors expressed VEGFR1, VEGFR2 and Glut-1 at membrane level, but only 15% of them showed PDGF-A staining. In addition, 34% of samples expressed p53 at nuclear level. VEGFR1 expression correlated with the expression of the other membrane receptors studied (p<0.05 Pearson test). Interestingly VEGFR2 and PDGF-A immunopositivity on ccRCC tumors could be associated with the presence of metastasis at diagnosis (p<0.05, Chi square test). On the other hand, the expression of membrane VEGFR2 correlated with tumor size (p<0.01 Pearson). No association was observed between the expression of these biomarkers and histological grade, Fuhrman classification or clinical stage. Kaplan-Meier curves and Log rank test showed that no one of the tumor markers studied were associated with DFS; however we observed that those patients who never relapsed were negative for VEGFR2 and Glut1 antigens.In conclusion, we found that some of the studied biomarkers could be associated with some clinical parameters. In particular, VEGFR2 and PDGF-A membrane immunopositivity was associated with metastatic disease. However, the presence of these antigens in ccRCC samples obtained from surgery did not predict disease-free survival. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5570. doi:1538-7445.AM2012-5570