Montreal Children's Hospital Research Institute, McGill University, Montreal, QC, Canada.
BJU Int. 2011 Feb;107(3):416-24. doi: 10.1111/j.1464-410X.2010.09569.x. Epub 2010 Aug 27.
To assess whether ageing processes influence angiogenesis in renal cell carcinoma (RCC) we carried out a pilot study of vascular properties in a series of archival primary kidney tumours in patients of different ages.
A cohort of patients with RCC was identified restrospectively, with an age range of 35-84 years. Paraffin-embedded, formalin-fixed sections of surgical tumour specimens were stained for endothelial (CD31, von Willebrand factor [vWF]), pericyte (alpha smooth muscle actin [SMA]) and leucocytic (CD45) markers, as well as for proliferative (Ki67) and angiogenic activity (tumour endothelial markers [TEMs], delta-like 4 [Dll4], Dll1, endothelial nitric oxide synthase [eNOS]). Vascular properties were compared between patients above and below 65 years of age.
Microvascular density (MVD) within capillary hot spots was generally higher in patients with non-metastatic clear-cell RCC (ccRCC; n = 21) than in those with metastatic RCC (mRCC; n= 9). Patients with ccRCC who were more than 65 years old showed significantly higher MVD than their younger (< 65 years) counterparts. There were dividing (Ki67-positive) endothelial and mural cells in both small (< 20 µm) capillary and large (> 20 µm), pre-capillary vessels, suggesting the involvement of both angiogenic and remodelling/arteriogenic processes. Tumour endothelial markers (TEM1, TEM7, TEM8), Notch ligands (Dll1, Dll4), and other molecular characteristics (eNOS) were analysed. Age-related differences were observed in the frequency of pre-capillary vessels expressing Dll1, which was significantly higher in tumours of younger patients (< 65 years), while eNOS was more prevalent among capillaries associated with ccRCC in older patients (>6 5 years).
The results of the present study suggest that age influences the structural and molecular properties of the tumour vasculature in ccRCC. We postulate that vascular ageing could also be relevant in the context of anti-angiogenic therapy.
为了评估衰老过程是否影响肾细胞癌（RCC）中的血管生成，我们对一系列不同年龄患者的存档原发性肾肿瘤的血管特性进行了一项初步研究。
我们回顾性地确定了一组 RCC 患者，年龄范围为 35-84 岁。对手术肿瘤标本的石蜡包埋、福尔马林固定切片进行内皮（CD31、血管性血友病因子[vWF]）、周细胞（α平滑肌肌动蛋白[SMA]）和白细胞（CD45）标志物以及增殖（Ki67）和血管生成活性（肿瘤内皮标志物[TEMs]、Delta-like 4 [Dll4]、Dll1、内皮型一氧化氮合酶[eNOS]）染色。比较了 65 岁以上和 65 岁以下患者的血管特性。
非转移性透明细胞 RCC（ccRCC；n=21）患者的毛细血管热点内微血管密度（MVD）普遍高于转移性 RCC（mRCC；n=9）患者。年龄超过 65 岁的 ccRCC 患者的 MVD 明显高于年龄较小（<65 岁）的患者。小（<20 µm）毛细血管和大（>20 µm）前毛细血管中均存在有丝分裂（Ki67 阳性）的内皮细胞和壁细胞，提示涉及血管生成和重塑/动脉生成过程。分析了肿瘤内皮标志物（TEM1、TEM7、TEM8）、Notch 配体（Dll1、Dll4）和其他分子特征（eNOS）。在表达 Dll1 的前毛细血管中观察到与年龄相关的差异，年轻患者（<65 岁）的肿瘤中 Dll1 的频率明显更高，而 eNOS 在老年患者（>65 岁）中与 ccRCC 相关的毛细血管中更为常见。
本研究结果表明，年龄影响 ccRCC 肿瘤血管的结构和分子特性。我们推测血管老化在抗血管生成治疗中也可能具有相关性。
