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

Histopathology. 2011 May;58(6):875-85. doi: 10.1111/j.1365-2559.2011.03845.x.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Neoplasm / metabolism
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases / metabolism
  • Carcinoma, Basal Cell / blood supply*
  • Carcinoma, Basal Cell / metabolism
  • Carcinoma, Basal Cell / pathology
  • Carcinoma, Squamous Cell / blood supply*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / pathology
  • Cell Proliferation
  • Disease Progression*
  • Female
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Immune System / drug effects
  • Immune System / physiopathology
  • Immunocompetence / physiology
  • Immunocompromised Host*
  • Immunosuppressive Agents / pharmacology
  • Kidney Transplantation / immunology*
  • Male
  • Middle Aged
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / physiopathology
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / physiopathology*
  • Retrospective Studies
  • Skin Neoplasms / blood supply*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antigens, Neoplasm
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Immunosuppressive Agents
  • Vascular Endothelial Growth Factor A
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases