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

Mackenzie K A, Miller A P, Hock B D, Gardner J, Simcock J W, Roake J A, Dachs G U, Robinson B A & Currie M J
(2011) Histopathology  58 , 875–885
Angiogenesis and host immune response contribute to the aggressive character of non‐melanoma skin cancers in renal transplant recipients Aims: 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). Methods and results: 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). Conclusions: This study demonstrates increased tumour angiogenesis in NMSC in RTRs, and suggests a role for VEGF‐A‐positive peritumoural leukocytes in suppressing NMSC development.