Microscopic analysis and significance of vascular architectural complexityin renal cell carcinoma

The objective of this study was to evaluate the utility of measuring microv essel fractal dimension (MFD) as a parameter of architectural microvascular complexity in localized renal cell carcinoma (RCC), Forty-nine patients wi th low-stage clear cell RCC were assessed in a 9-year follow-up retrospecti ve study, Tumor vessels were visualized with the endothelial marker CD34, T umor microvessel density (MVD) was measured by computerized morphometry. Fr actal analysis of the RCC microvascular network was performed and the MFD w as computed in each case. Correlation between tumor vascular parameters, hi stological grade, extent of tumor necrosis and patient survival were tested by uni- and multivariate analyses. A significant correlation was found bet ween tumor grade and decreased survival (P = 0.04), The extent of macroscop ic tumor necrosis also significantly correlated with poor prognosis (P = 0. 0001), Survival analysis revealed a significantly higher MVD in patients wh o survived longer than 5 years as compared with those who died before the e nd of the 5-year follow-up period (MVD = 10.8 +/- 4.7% versus 6.4 +/- 3.7%; P = 0.03), MVD was also inversely associated with the extent of tumor necr osis (P = 0.03), Microvessel fractal dimension was significantly higher in low- as compared with high-grade tumors (1.55 +/- 0.11 versus 1.45 +/- 0.15 ; P = 0.03), Survival analysis revealed a significantly higher MFD in those who lived >5 years as compared with those who died earlier (1.56 +/- 0.11 versus 1.46 +/- 0.15; P = 0.02), The MFD was inversely associated with the extent of tumor necrosis (P = 0.01), Multivariate analysis revealed that th e MFD was the only significant factor to correlate with tumor necrosis, and that tumor necrosis was the only independent predictor of patient survival . These results indicate that the analysis of MFD as a marker of tumor micr ovascular complexity may provide important prognostic information as well a s novel insight into the biology of tumor angiogenesis.