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Microscopic Analysis and Significance of Vascular Architectural Complexity in Renal Cell Carcinoma

Departments of Pathology [E. S., A. B., Y. S., S. K., M. B. R.] and Urology [A. S.], Carmel Medical Center and Technion-Bruce Rappaport Faculty of Medicine, Haifa 34362, Israel

The objective of this study was to evaluate the utility of measuring microvessel fractal dimension (MFD) as a parameter of architectural microvascular complexity in localized renal cell carcinoma (RCC). Forty-nine patients with low-stage clear cell RCC were assessed in a 9-year follow-up retrospective study. Tumor vessels were visualized with the endothelial marker CD34. Tumor microvessel density (MVD) was measured by computerized morphometry. Fractal analysis of the RCC microvascular network was performed and the MFD was computed in each case. Correlation between tumor vascular parameters, histological grade, extent of tumor necrosis and patient survival were tested by uni- and multivariate analyses. A significant correlation was found between tumor grade and decreased survival (P = 0.04). The extent of macroscopic tumor necrosis also significantly correlated with poor prognosis (P = 0.0001). Survival analysis revealed a significantly higher MVD in patients who survived longer than 5 years as compared with those who died before the end 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 necrosis (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 the 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 microvascular complexity may provide important prognostic information as well as novel insight into the biology of tumor angiogenesis.

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