Vr. Litle et al., Angiogenesis, proliferation, and apoptosis in anal high-grade squamous intraepithelial lesions, DIS COL REC, 43(3), 2000, pp. 346-352
PURPOSE: Management of anal high-grade squamous intraepithelial lesions is
controversial. Anal and cervical high-grade squamous intraepithelial lesion
s are similar in that they occur in transitional squamous epithelium, are a
ssociated with human papilloma virus infection, and have in creased inciden
ce in the immunocompromised population. Ablation of cervical high-grade squ
amous intraepithelial lesions is preferred, but similar ablation or excisio
n of anal high-grade squamous intraepithelial lesions may compromise bowel
control; thus, there is a need to define the malignant potential of anal hi
gh-grade squamous intraepithelial lesions. METHODS: We analyzed 50 paraffin
sections of normal anoderm, anal low-grade squamous intraepithelial lesion
s, high-grade squamous intraepithelial lesions, and anal squamous-cell carc
inoma. Microvessels were detected immunohistochemically with von Willebrand
factor and counted manually along the epithelial-stromal junction. Prolife
ration and apoptosis were determined in the epithelial cells with MIB-1 ant
ibody immunostaining and the terminal deoxynucleotidyl transferase-mediated
digoxigenin-11-dUTP nick end labeling, respectively. RESULTS: Microvascula
r density was significantly greater in anal high-grade squamous intraepithe
lial lesions (mean, 0.50 vessels/cm) vs. normal anoderm (mean, 0.21 vessels
/cm; P = 0.0017, Mann-Whitney U test). The proliferative percentages were g
reater in low-grade squamous intraepithelial lesions, high-grade squamous i
ntraepithelial lesions, and squamous-cell carcinoma (mean, 20.4, 21.8, and
23.6 percent) vs. normal anoderm (mean, 14.4 percent), although not signifi
cantly (P = 0.06, Kruskal-Wallis statistic). Although the mean proliferativ
e proportions were similar in low-grade squamous intraepithelial lesions an
d high-grade squamous intraepithelial lesions, the apoptotic proportion was
lower for high-grade squamous intraepithelial lesions than low-grade squam
ous intraepithelial lesions (10.13 vs. 19.96 percent, respectively; P = NS,
Mann-Whitney U test). CONCLUSIONS: Angiogenesis, increased proliferation,
and decreased apoptosis occur in anal high-grade squamous intraepithelial l
esions as they do in the cervix before the development of malignancy. These
biologic markers support the importance of anal high-grade squamous intrae
pithelial lesions as a potential premalignant lesion warranting surgical in
tervention.