title: Angiogenesis and host immune response contribute to the aggressive character of non-melanoma skin cancers in renal transplant recipients.
abstract: OBJECTIVE
  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).
  
  
  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.
authors.affiliation: Angiogenesis and Cancer Research Group, University of Otago Christchurch, Christchurch, New Zealand.
authors.forename: Katarzyna Anna
authors.initials: KA
authors.lastname: Mackenzie
authors.forename: Andrew Peter
authors.initials: AP
authors.lastname: Miller
authors.forename: Barry David
authors.initials: BD
authors.lastname: Hock
authors.forename: Jacqui
authors.initials: J
authors.lastname: Gardner
authors.forename: Jeremy William
authors.initials: JW
authors.lastname: Simcock
authors.forename: Justin Allan
authors.initials: JA
authors.lastname: Roake
authors.forename: Gabi Ursula
authors.initials: GU
authors.lastname: Dachs
authors.forename: Bridget Anne
authors.initials: BA
authors.lastname: Robinson
authors.forename: Margaret Jane
authors.initials: MJ
authors.lastname: Currie
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000378:metabolism; D002280:Basal Cell Carcinoma / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D018450:Disease Progression; D005260:Female; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D007107:Immune System / Q000187:drug effects / Q000503:physiopathology; D007121:Immunocompetence / Q000502:physiology; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents / Q000494:pharmacology; D016030:Kidney Transplantation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000503:physiopathology; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology*; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000951:Antigens, Neoplasm; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007166:Immunosuppressive Agents; D042461:Vascular Endothelial Growth Factor A; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases