Department of Nephro-Urology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan,
Virchows Arch. 2013 Nov;463(5):673-9. doi: 10.1007/s00428-013-1463-8. Epub 2013 Aug 25.
Angiogenesis plays an important role in cancer progression in many types of cancer. Evaluation of angiogenesis is often performed, but the optimal methodology for human cancer has not been agreed upon. As adequate evaluation of angiogenesis in cancer tissues might be important for prediction of prognosis and treatment decisions, we evaluated angiogenesis semiquantitatively by assessing microvessel density (MVD) in urothelial cancer of the upper urinary tract (UC-UUT). We compared the performance of three endothelial cell markers (CD31, CD34, and CD105) on formalin-fixed tissues from 122 patients diagnosed with UC-UUT without metastasis. Vascular endothelial growth factor (VEGF)-A expression was also evaluated immunohistochemically. Correlations between MVD with each marker and pT stage, grade, survival, and VEGF-A expression were investigated. Mean (standard deviation) MVD as estimated by immunohistochemical staining with anti-CD31, anti-CD34, and anti-CD105 were 47.1 (17.9)/high-power field (HPF), 70.9 (19.5)/HPF, and 31.2 (16.7)/HPF, respectively. Although all MVDs were significantly associated with pT stage and grade, CD105-MVD showed the strongest association. Similarly, CD105-MVD showed the strongest correlation with VEGF-A expression (r = 0.530, p < 0.001). Although all MVDs were associated with metastasis-free survival and cause-specific survival on univariate analysis, only CD105-MVD was retained as an independent predictor in multivariate analysis including pT stage and grade. CD105-MVD may be the preferred marker for semiquantitative assessment of angiogenesis in patients with UC-UUT.
血管生成在许多类型的癌症的癌症进展中起着重要作用。通常会进行血管生成的评估,但对于人类癌症的最佳方法尚未达成共识。由于在癌症组织中充分评估血管生成可能对预测预后和治疗决策很重要,因此我们通过评估上尿路上皮癌(UC-UUT)的微血管密度(MVD)来半定量评估血管生成。我们比较了三种内皮细胞标志物(CD31、CD34 和 CD105)在 122 例无转移 UC-UUT 患者的福尔马林固定组织中的表现。还通过免疫组织化学评估了血管内皮生长因子(VEGF)-A 的表达。研究了 MVD 与每个标志物之间与 pT 分期、分级、生存和 VEGF-A 表达的相关性。用抗-CD31、抗-CD34 和抗-CD105 进行免疫组织化学染色估计的平均(标准差)MVD 分别为 47.1(17.9)/高倍视野(HPF)、70.9(19.5)/HPF 和 31.2(16.7)/HPF。尽管所有 MVD 均与 pT 分期和分级显著相关,但 CD105-MVD 相关性最强。同样,CD105-MVD 与 VEGF-A 表达的相关性最强(r=0.530,p<0.001)。尽管所有 MVD 在单变量分析中均与无复发生存和特定原因生存相关,但只有 CD105-MVD 在包括 pT 分期和分级的多变量分析中保留为独立预测因子。CD105-MVD 可能是评估 UC-UUT 患者血管生成的首选标志物。