Serologic angiogenesis factors and microvascular density in renal cell carcinoma: two independent parameters

Renal Cell Carcinoma (RCC) is characterized by high intratumoral microvascular density (iMVD) and significantly elevated serologic titers of angiogenesis factors, basic fibroblast growth factor (bFGF), vascular endothelial growth factor (vEGF) and angiogenin (Ag). The goal of the present study was to find whether a correlation exists between any of these factors and intratumoral microvascular density (iMVD). Serologic angiogenesis factors were determined directly before nephrectomy of a tumorous kidney in 12 patients (average age: 67.6 years [49-78] with localized clear-cell RCC (Robson I-II) (Quantikine', R&D Systems Europe, Abington, UK). Sections were taken in each case from the microscopically most aggressive area of the tumorous kidney preparations. Staining was carried out with a primary antibody against CD31 (DAKO M 0823, Hamburg, Germany). iMVD was counted at 160x magnification at five "hot spots" 200 x 200 microns in size, and the individual factors were then correlated with the areas of maximum and average iMVD (iMVDmax, iMVD-d). Average concentrations of 38 pg/ml +/- 68 were found for bFGF, 712 pg/ml +/- 791 for vEGF, and 358 ng/ml +/- 97 for Ag. iMVDmax was 20 +/- 11 per area, iMVD-d was 410/mm2 +/- 243. No correlation was found between microvascular density and serologic angiogenesis factors for any parameter. Actual tumor vascularization, expressed as iMVD, was not correlated with the 3 angiogenesis parameters which were studied. On the one hand, this raises the question whether angiogenesis can be measured at all with these parameters; on the other, it remains nuclear whether the continuous process of angiogenesis can be registered at all by chronologic, specific factor analysis.