The role of macrophages in angiogenesis. Comparison between HIV+ and HIV- populations with anal dysplasia and anal cancer.
BACKGROUND
While macrophages (CD68+) have been associated with angiogenesis in some inflammatory and neoplastic processes by increasing the release of vascular endothelial growth factor (VEGF), their role in anal intraepithelial neoplasia (AIN) and anal squamous cell carcinoma has not been established. This study records macrophage infiltration in anal pre-invasive and invasive lesions in HIV+ and HIV- populations, and determines their relationship with angiogenesis.


METHODS
Sixty patients (31 HIV+) with AIN and anal SCC were studied. Paraffin sections were stained for CD68, VEGF and von Willebrand factor. The density of CD68 cells, the expression of VEGF and angiogenesis were quantified, and compared amongst groups and between HIV+ and HIV- populations.


RESULTS
All three parameters increased linearly as the lesions became more dysplastic, in HIV+ and HIV- groups. The CD68 count was statistically lower in HIV+ (p<0.005) compared with HIV- groups, while the differences in VEGF expression and in angiogenesis were not significant between HIV+ and HIV- populations.


CONCLUSIONS
There was a significant decrease of macrophage infiltrate in the HIV+ group. The relative increase in VEGF expression and angiogenesis in the face of lower macrophage infiltration in HIV+ patients may be explained either by a greater release of angiogenic factors by macrophages, or by VEGF expression not being solely dependent on macrophage activation.
Mullerat
Jose
J
University Department of Surgery, Royal Free and University College Medical School, Pond Street, London NW3 2QG, UK. p.mullerat@medsch.ucl.ac.uk
Perrett
Christopher W
CW
Deroide
Florence
F
Winslet
Mark C
MC
Bofill
Margarita
M
Poulters
Leonard W
LW
D001003:Anal Canal / Q000098:blood supply / Q000473:pathology; D015703:Antigens, CD / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D001004:Anus Diseases / Q000473:pathology / Q000821:virology; D001005:Anus Neoplasms / Q000098:blood supply* / Q000821:virology*; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000821:virology*; D018450:Disease Progression; D015658:HIV Infections / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology / Q000473:pathology / Q000502:physiology*; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D011230:Precancerous Conditions / Q000098:blood supply / Q000821:virology; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis; D014860:Warts / Q000473:pathology / Q000821:virology; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D042461:Vascular Endothelial Growth Factor A; C067980:CD68 antigen, human; D000097382:CD68 Molecule