Age-related properties of the tumour vasculature in renal cell carcinoma

OBJECTIVE 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. PATIENTS AND METHODS 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. RESULTS 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 Âμm) capillary and large (>20 Âμm), 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 (>65 years). CONCLUSIONS 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.