Sabo E, Boltenko A, Sova Y, Stein A, Kleinhaus S, Resnick M B
Department of Pathology, Carmel Medical Center and Technion-Bruce Rappaport Faculty of Medicine, Haifa, Israel.
Clin Cancer Res. 2001 Mar;7(3):533-7.
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.
本研究的目的是评估测量微血管分形维数（MFD）作为局限性肾细胞癌（RCC）中微血管结构复杂性参数的效用。在一项为期9年的随访回顾性研究中，对49例低分期透明细胞RCC患者进行了评估。用内皮标志物CD34使肿瘤血管可视化。通过计算机形态学测量肿瘤微血管密度（MVD）。对RCC微血管网络进行分形分析，并计算每例的MFD。通过单因素和多因素分析测试肿瘤血管参数、组织学分级、肿瘤坏死程度与患者生存率之间的相关性。发现肿瘤分级与生存率降低之间存在显著相关性（P = 0.04）。宏观肿瘤坏死程度也与预后不良显著相关（P = 0.0001）。生存分析显示，存活超过5年的患者的MVD显著高于在5年随访期结束前死亡的患者（MVD = 10.8 +/- 4.7% 对 6.4 +/- 3.7%；P = 0.03）。MVD也与肿瘤坏死程度呈负相关（P = 0.03）。低级别肿瘤的微血管分形维数显著高于高级别肿瘤（1.55 +/- 0.11对1.45 +/- 0.15；P = 0.03）。生存分析显示，存活超过5年的患者的MFD显著高于早期死亡的患者（1.56 +/- 0.11对1.46 +/- 0.15；P = 0.02）。MFD与肿瘤坏死程度呈负相关（P = 0.01）。多因素分析显示，MFD是与肿瘤坏死相关的唯一显著因素，而肿瘤坏死是患者生存的唯一独立预测因子。这些结果表明，将MFD作为肿瘤微血管复杂性的标志物进行分析可能提供重要的预后信息以及对肿瘤血管生成生物学的新见解。
