title: Immunohistochemical expression of p16 and Ki-67 correlates with degree of anal intraepithelial neoplasia.
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.
authors.affiliation: Department of Pathology, Duke University, Durham, NC, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Bean
authors.forename: Isam
authors.initials: I
authors.lastname: Eltoum
authors.forename: Debra K
authors.initials: DK
authors.lastname: Horton
authors.forename: Leisa
authors.initials: L
authors.lastname: Whitlow
authors.forename: David C
authors.initials: DC
authors.lastname: Chhieng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001005:Anus Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000378:metabolism / Q000821:virology; D005260:Female; D019942:Genes, p16; D049670:History, 17th Century; D006801:Humans; D007150:Immunohistochemistry; D019394:Ki-67 Antigen / Q000378:metabolism*; D008297:Male; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000378:metabolism; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D012680:Sensitivity and Specificity; D014412:Tumor Virus Infections / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen