Angiogenesis and host immune response contribute to the aggressive character of non-melanoma skin cancers in renal transplant recipients

Abstract

The aim of this study was to determine the contribution of tumour angiogenesis to the aggressive growth of non-melanoma skin cancers (NMSCs) in renal transplant recipients (RTRs). The study cohort included RTRs (n = 38) with formalin-fixed paraffin-embedded tumour samples available from first post-transplant NMSC (NMSC1) surgically excised at Christchurch Hospital, New Zealand, from 1997 to 2007. Comparable samples excised from immunocompetent individuals (ICIs) (n = 36) were selected to accommodate confounding factors. Markers of tumour angiogenesis were evaluated by immunohistochemistry, and analysed for associations with clinicopathological variables. As compared with ICIs, RTRs had a higher proportion of tumours with high microvessel density (P = 0.008), high proliferating capillary index (P < 0.0001) and low microvessel pericyte coverage index (P < 0.0001), and RTRs had a shorter cumulative second NMSC (NMSC2)-free interval (P < 0.0001). ICIs had a higher proportion of tumours with a 'marked' number of vascular endothelial growth factor (VEGF)-A-positive leukocytes than RTRs (P = 0.04), and RTRs with a 'moderate/marked' number of VEGF-A-positive leukocytes had longer cumulative NMSC2-free intervals than those with a 'minimum' number (P = 0.02). This study demonstrates increased tumour angiogenesis in NMSC in RTRs, and suggests a role for VEGF-A-positive peritumoural leukocytes in suppressing NMSC development.