Gelb A B, Sudilovsky D, Wu C D, Weiss L M, Medeiros L J
Department of Anatomic Pathology, University of California, San Francisco, USA.
Cancer. 1997 Nov 1;80(9):1768-75. doi: 10.1002/(sici)1097-0142(19971101)80:9<1768::aid-cncr11>3.0.co;2-3.
The prognostic values of intratumoral microvessel density (iMVD), tumor cell proliferation rate, DNA content (ploidy), and p53 protein expression are controversial or have not been well studied in patients with renal cell carcinoma (RCC) confined to the kidney.
A uniform group of 52 clear cell (conventional) RCCs confined to the kidney (classified as T1N0M0 or T2N0M0) were analyzed for iMVD, MIB-1 score, DNA content, S-phase fraction, and p53 protein expression by immunohistochemical methods or flow cytometry. iMVD was evaluated in a single area (X200, 1.15 mm2) representative of the highest MVD (neovascular "hot spot") after independently highlighting endothelial cells with antibodies specific for factor VIII-related antigen (F8/86) and CD31 (JC/70A). The MIB-1 antibody (Ki-67 antigen) score was used as a marker for the tumor cell proliferation rate. DNA content and S-phase fraction were determined by flow cytometry using paraffin embedded tissue. p53 expression was assessed using the D07 antibody.
The median time of clinical follow-up was > 9 years. Eleven patients died of disease; the median time to death was 26 months. iMVD counts using antifactor VIII and anti-CD31 were tightly correlated (correlation coefficient = 0.89). S-phase fraction was higher in aneuploid tumors than in diploid tumors (mean, 12.4% vs. 4.3%; P = 0.01). Using univariate survival analyses, tumor size (stage classification pT1 vs. PT2; P = 0.01) and nuclear grade (P = 0.04) were associated with shortened survival. No statistically significant differences in survival were found for iMVD, MIB-1 score, DNA content, S-phase fraction, or p53 expression. Only two cases strongly expressed p53 protein; both tumors were of high nuclear grade. Using multivariate survival analyses, nuclear grade and tumor size were the only independent prognostic factors (best model P = 0.002).
In this study, nuclear grade and tumor size were found to be independent predictors of survival in locally confined clear cell (conventional) RCC, as has been shown previously for locally confined RCC in general. MIB-1 score, iMVD counts, DNA content, S-phase fraction, and p53 expression did not contribute additional prognostic information.
肿瘤内微血管密度（iMVD）、肿瘤细胞增殖率、DNA含量（倍体）和p53蛋白表达的预后价值存在争议，或在局限于肾脏的肾细胞癌（RCC）患者中尚未得到充分研究。
采用免疫组织化学方法或流式细胞术，对一组统一的52例局限于肾脏的透明细胞（传统型）RCC（分类为T1N0M0或T2N0M0）进行iMVD、MIB-1评分、DNA含量、S期分数和p53蛋白表达分析。在用针对因子VIII相关抗原（F8/86）和CD31（JC/70A）的特异性抗体独立标记内皮细胞后，在代表最高MVD的单个区域（X200，1.15平方毫米）评估iMVD。MIB-1抗体（Ki-67抗原）评分用作肿瘤细胞增殖率的标志物。使用石蜡包埋组织通过流式细胞术测定DNA含量和S期分数。使用D07抗体评估p53表达。
临床随访的中位时间>9年。11例患者死于疾病；死亡的中位时间为26个月。使用抗因子VIII和抗CD31的iMVD计数密切相关（相关系数=0.89）。非整倍体肿瘤的S期分数高于二倍体肿瘤（平均值分别为12.4%和4.3%；P=0.01）。使用单因素生存分析，肿瘤大小（分期分类pT1与PT2；P=0.01）和核分级（P=0.04）与生存期缩短相关。iMVD、MIB-1评分、DNA含量、S期分数或p53表达在生存率方面未发现统计学上的显著差异。仅2例强烈表达p53蛋白；这两个肿瘤均为高核分级。使用多因素生存分析，核分级和肿瘤大小是仅有的独立预后因素（最佳模型P=0.002）。
在本研究中，核分级和肿瘤大小被发现是局部局限的透明细胞（传统型）RCC生存的独立预测因素，正如之前总体上针对局部局限的RCC所显示的那样。MIB-1评分、iMVD计数、DNA含量、S期分数和p53表达未提供额外的预后信息。
