title: Angiogenesis, proliferation, and apoptosis in anal high-grade squamous intraepithelial lesions.
abstract: OBJECTIVE
  Management of anal high-grade squamous intraepithelial lesions is controversial. Anal and cervical high-grade squamous intraepithelial lesions are similar in that they occur in transitional squamous epithelium, are associated with human papilloma virus infection, and have increased incidence in the immunocompromised population. Ablation of cervical high-grade squamous intraepithelial lesions is preferred, but similar ablation or excision of anal high-grade squamous intraepithelial lesions may compromise bowel control; thus, there is a need to define the malignant potential of anal high-grade squamous intraepithelial lesions.
  
  
  METHODS
  We analyzed 50 paraffin sections of normal anoderm, anal low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and anal squamous-cell carcinoma. Microvessels were detected immunohistochemically with von Willebrand factor and counted manually along the epithelial-stromal junction. Proliferation and apoptosis were determined in the epithelial cells with MIB-1 antibody immunostaining and the terminal deoxynucleotidyl transferase-mediated digoxigenin-11-dUTP nick end labeling, respectively.
  
  
  RESULTS
  Microvascular density was significantly greater in anal high-grade squamous intraepithelial 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 greater in low-grade squamous intraepithelial lesions, high-grade squamous intraepithelial lesions, and squamous-cell carcinoma (mean, 20.4, 21.8, and 23.6 percent) vs. normal anoderm (mean, 14.4 percent), although not significantly (P = 0.06, Kruskal-Wallis statistic). Although the mean proliferative proportions were similar in low-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions, the apoptotic proportion was lower for high-grade squamous intraepithelial lesions than low-grade squamous 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 lesions as they do in the cervix before the development of malignancy. These biologic markers support the importance of anal high-grade squamous intraepithelial lesions as a potential premalignant lesion warranting surgical intervention.
authors.affiliation: Department of Surgery, University of California at San Francisco, USA.
authors.forename: V R
authors.initials: VR
authors.lastname: Litle
authors.forename: J D
authors.initials: JD
authors.lastname: Leavenworth
authors.forename: T M
authors.initials: TM
authors.lastname: Darragh
authors.forename: L A
authors.initials: LA
authors.lastname: Kosinski
authors.forename: D H
authors.initials: DH
authors.lastname: Moore
authors.forename: K K
authors.initials: KK
authors.lastname: Smith-McCune
authors.forename: R S
authors.initials: RS
authors.lastname: Warren
authors.forename: J M
authors.initials: JM
authors.lastname: Palefsky
authors.forename: M L
authors.initials: ML
authors.lastname: Welton
mesh_terms: D001003:Anal Canal / Q000098:blood supply / Q000473:pathology; D001005:Anus Neoplasms / Q000098:blood supply* / Q000473:pathology; D017209:Apoptosis / Q000502:physiology*; D001706:Biopsy; D002278:Carcinoma in Situ / Q000098:blood supply* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000098:blood supply* / Q000473:pathology; D002455:Cell Division / Q000502:physiology*; D006801:Humans; D008833:Microcirculation / Q000473:pathology; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000473:pathology*