Lymphangiogenesis in kidney cancer: expression of VEGF-C, VEGF-D and VEGFR-3 in clear cell and papillary renal cell carcinoma.

The vascular endothelial growth factors VEGF-C, VEGF-D and its receptor, VEGFR-3, are overexpressed in different malignancies and associated with lymph node metastasis and poor prognosis. We analysed these factors in clear cell (ccRCC) and papillary (pRCC) renal cell carcinoma (RCC). The results were correlated with various clinicopathological parameters (CPP). We constructed a tissue microarray with tumor samples of 135 (81%) ccRCC and 31 (19%) pRCC. After immunohistochemical staining using polyclonal antibodies for VEGF-C, VEGF-D and VEGFR-3, a semiquantitative analysis was performed to determine the levels of expression. The results were compared between the two subgroups and were correlated with CPP. In the two subgroups the expression of VEGF-C was significantly correlated with that of VEGF-D (p<0.001). There was an increased expression of VEGF-C in 11% of ccRCC and 36% of pRCC (p=0.002). VEGF-D expression was positive by means of analysis in 22% of ccRCC and 42% of pRCC (p=0.039). There was no significant difference regarding the expression of VEGFR-3 between the subgroups (44% ccRCC and 61% pRCC, p=0.11). No correlation was found between the expression of the analysed parameters and CPP (TNM, grading, progression-free survival and overall survival) in either the entire group or in the two subgroups. In summary, ccRCC and pRCC show a different expression pattern of the analysed lymphangiogenic factors. Further studies are necessary to confirm these results and to determine whether the VEGF-C/VEGF-D/VEGFR-3-axis can play a role as a prognostic tool or a target for therapeutic intervention in renal cell carcinoma.