Yildiz Esin, Ayan Semih, Goze Fahrettin, Gokce Gokhan, Gultekin Emin Y
Department of Pathology, Cumhuriyet University, Sivas, Turkey.
BJU Int. 2008 Mar;101(6):758-64. doi: 10.1111/j.1464-410X.2007.07318.x. Epub 2007 Dec 7.
To clarify the significance of microvessel density (MVD) in a retrospective investigation the relationship between the pattern of MVD (reflecting angiogenesis), and tumour stage, grade, size, and occurrence of microvessel invasion (MVI), metastasis, and cancer-specific survival (CSS) in patients who had surgery for renal cell carcinoma (RCC).
Vessels were labelled in sections of formalin-fixed, paraffin-embedded tissues from 54 RCCs by CD34 immunohistochemistry. The mean MVD, expressed as the number of vessels per 10 high-power fields (HPF, x400) were measured for each case. In addition, all pathological slides were reviewed for the presence and absence of MVI. The prognostic value of MVD and MVI was then evaluated, and correlated with the usual prognostic variables, tumour metastasis and CSS.
In a univariate analysis of CSS, the MDV tended to be lower as stage increased from pT1 to pT3, and as grade increased from G1 to G4, although it was statistically significant only for stage (P < 0.001 and 0.050, respectively). The mean MVD was higher in 42 nonmetastatic than in 12 metastatic tumours, and in 33 tumours associated with MVI than in 21 with no MVI (P < 0.001). The mean MVD was also lower and significantly different for 28 large than 26 small tumours (P = 0.005). The survival rate of patients with tumours that were small, low-stage, of higher MVD, with no MVI and metastasis was significantly higher than that of patients with large, high-stage, low MVD, with MVI and metastatic tumours (all P < 0.001). MVI was significantly more common with a decreasing trend in MVD and the presence of metastasis (Spearman rank correlation r(s) = -0.68, P = 0.01, and r(s) = 0.39, P = 0.01, respectively). Independent prognostic factors in a multivariate analysis were: in all patients with RCC, tumour stage (P = 0.013) and metastasis (P = 0.028); in those with low MVD, MVI (P = 0.004) and metastases (P = 0.016); in those with no MVI, stage (P = 0.020); in those with MVI, MVD (P = 0.001); in those with no metastases, stage (P = 0.045); and in those with metastases, MVD (P < 0.001). No independent predictor was identified in patients with high MVD. In patients with no metastases there was a significantly shorter median CSS time in RCCs with low MVD and with MVI (P = 0.004 for both). Similarly, patients who had grade 3-4 tumours, vs those with lower MVD and with MVI, had a significantly shorter median CSS (P = 0.020 for MVD, and 0.01 for MVI).
This study suggested that MVD in RCC was inversely associated with MVI, tumour metastasis, patient survival and tumour diameter and stage, from the usual prognostic variables, but MVD was not an independent prognostic factor in multivariate analysis for all patients with RCC. Low MVD and the presence of MVI appears to be a marker for identifying patients with an adverse prognosis.
在一项回顾性研究中，明确微血管密度（MVD）在肾细胞癌（RCC）手术患者中所反映的血管生成模式与肿瘤分期、分级、大小、微血管侵犯（MVI）的发生、转移及癌症特异性生存（CSS）之间关系的意义。
采用CD34免疫组化法对54例RCC的福尔马林固定、石蜡包埋组织切片中的血管进行标记。测量每例患者的平均MVD，以每10个高倍视野（HPF，×400）中的血管数量表示。此外，复查所有病理切片以确定有无MVI。然后评估MVD和MVI的预后价值，并将其与常见的预后变量、肿瘤转移及CSS进行关联分析。
在CSS的单因素分析中，随着分期从pT1增加到pT3以及分级从G1增加到G4，MDV有降低趋势，不过仅分期具有统计学意义（分别为P < 0.001和0.050）。42例非转移性肿瘤的平均MVD高于12例转移性肿瘤，33例伴有MVI的肿瘤的平均MVD高于21例无MVI的肿瘤（P < 0.001）。28例大肿瘤的平均MVD也低于26例小肿瘤，且差异有统计学意义（P = 0.005）。肿瘤小、分期低、MVD高、无MVI和转移的患者生存率显著高于肿瘤大、分期高、MVD低、有MVI和转移的患者（所有P < 0.001）。MVI在MVD降低及存在转移时显著更常见（Spearman等级相关系数r(s)分别为 - 0.68，P = 0.01和r(s) = 0.39，P = 0.01）。多因素分析中的独立预后因素为：在所有RCC患者中，肿瘤分期（P = 0.013）和转移（P = 0.028）；在MVD低的患者中，MVI（P = 0.004）和转移（P = 0.016）；在无MVI的患者中，分期（P = 0.020）；在有MVI的患者中，MVD（P = 0.001）；在无转移的患者中，分期（P = 0.045）；在有转移的患者中，MVD（P < 0.001）。在MVD高的患者中未发现独立预测因素。在无转移的患者中，MVD低且有MVI的RCC患者的CSS中位时间显著缩短（两者均为P = 0.004）。同样，3 - 4级肿瘤患者与MVD低且有MVI的患者相比，CSS中位时间显著缩短（MVD为P = 0.020，MVI为P = 0.01）。
本研究提示，RCC中的MVD与MVI、肿瘤转移、患者生存及肿瘤直径和分期呈负相关，是常见的预后变量，但在所有RCC患者的多因素分析中，MVD并非独立预后因素。低MVD及存在MVI似乎是识别预后不良患者的一个标志物。
