Angiogenesis, proliferation, and apoptosis in anal high-grade squamous intraepithelial lesions

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.