Immunohistochemical expression of p16 and Ki-67 correlates with degree of anal intraepithelial neoplasia

Am J Surg Pathol. 2007 Apr;31(4):555-61. doi: 10.1097/PAS.0b013e31802ca3f4.

Abstract

Anal intraepithelial neoplasia (AIN) is a human papilloma virus related lesion. It has been shown that infection with high-risk human papilloma virus results in up-regulation of p16 and increased cellular proliferation. The objective of this study is to correlate p16 expression and cellular proliferation measured by Ki-67 staining with the degree of dysplasia in the anal canal and to determine the efficacy of these markers in diagnosing high-grade AIN. Seventy-five anal specimens from 55 patients (37 men; 18 women; mean age: 48 y; median: 44 y; range 25 to 96 y) were studied including 35 normal/reactive lesions, 23 low-grade AIN (AIN I and condyloma), and 17 high-grade AIN (AIN II and III). Immunostaining for p16 and Ki-67 was performed. Expression of p16 in AIN correlated with that of Ki-67 (P<0.001). High-grade AIN often demonstrated p16 staining in more than one-third of the thickness of the epithelium in a diffuse/continuous fashion. p16 expression in low-grade AIN was often restricted to the lower 1/3 of the epithelium and/or was focal and discontinuous. The expression of both p16 and Ki-67 correlated with the degree of dysplasia (P<0.01). When positive p16 staining was defined as the presence of diffuse/continuous staining in more than one-third of the thickness of epithelium, the sensitivity, specificity, and accuracy of p16 as a marker for diagnosing high-grade AIN were 76%, 86%, and 84%, respectively. When positive Ki-67 staining was defined as the presence of nuclear staining in more than 25% of the cells in more than one-third of the thickness of epithelium, the sensitivity, specificity, and accuracy of Ki-67 as a marker for diagnosing high-grade AIN were 71%, 84%, and 83% respectively. Both p16 and Ki-67 are reliable markers for diagnosing high-grade AIN.

Publication types

  • Historical Article

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anus Neoplasms / diagnosis*
  • Anus Neoplasms / metabolism
  • Anus Neoplasms / virology
  • Biomarkers, Tumor / analysis
  • Carcinoma, Squamous Cell / diagnosis
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / virology
  • Female
  • Genes, p16*
  • History, 17th Century
  • Humans
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism*
  • Male
  • Papillomavirus Infections / diagnosis*
  • Papillomavirus Infections / metabolism
  • Precancerous Conditions / diagnosis*
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / virology
  • Sensitivity and Specificity
  • Tumor Virus Infections / diagnosis*
  • Tumor Virus Infections / metabolism

Substances

  • Biomarkers, Tumor
  • Ki-67 Antigen