title: The utility of p16(Ink4a) in discriminating between cervical intraepithelial neoplasia 1 and nonneoplastic equivocal lesions of the cervix.
abstract: BACKGROUND
  The protein p16(Ink4a) is overexpressed in cervical lesions associated with high-risk human papillomavirus (HPV) subtypes 16 and 18, but not in low-risk HPV subtypes 6 and 11 or non-HPV-associated cervical lesions.
  
  
  OBJECTIVE
  To determine whether p16(Ink4a) expression in equivocal cervical lesions helps distinguish atypical non-HPV changes from HPV-related changes.
  
  
  METHODS
  One hundred ninety-one cervical lesions, including 81 cervical intraepithelial neoplasia 1, 52 squamous metaplasia, 33 cellular features suggestive of HPV-related change, 9 reserve cell hyperplasia, 4 microglandular hyperplasia, and 12 inflammatory cervicitis, were randomly selected from archival cervical biopsy specimens. All 191 samples were studied with p16(Ink4a) (JC8 monoclonal antibody). Reactivity for p16(Ink4a) was scored on a 3-tier system as follows: negative, 0% to 5% cells reactive; focal/scattered positive, greater than 5% and less than or equal to 80% cells reactive; diffuse positive, greater than 80% cells reactive. Reactivity was based on normal/reactive cervical specimens where anti-p16 antibody was negative/weakly expressed in non-cervical epithelial cells. Cervical intraepithelial neoplasia 1 lesions not reactive for p16(Ink4a) were investigated for the presence of high-risk HPV by real-time polymerase chain reaction.
  
  
  RESULTS
  No p16(Ink4a) reactivity was detected in the cervical lesions associated with atypical non-HPV change. Eleven of the cervical intraepithelial neoplasia 1 lesions showed focal/scattered reactivity expression for p16(Ink4a), and 19 of the CIN 1 lesions had diffuse reactivity. Fifty of 51 of the CIN 1 lesions negative for p16(Ink4a) were real-time polymerase chain reaction negative for the presence of high-risk HPV; 1 was real-time polymerase chain reaction positive for high-risk HPV.
  
  
  CONCLUSIONS
  The data support the routine use of p16(Ink4a) immunohistochemical evaluation of cervical biopsy specimens for better discrimination of non-HPV-associated lesions from HPV-related lesions.
authors.affiliation: Department of Pathology, College of Medicine, University of Florida, 1600 SW Archer Rd, Gainesville, FL 32610-0275, USA. redmanrs@yahoo.com
authors.forename: Rachel
authors.initials: R
authors.lastname: Redman
authors.forename: Irina
authors.initials: I
authors.lastname: Rufforny
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Wilkinson
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Massoll
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004279:DNA, Viral / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007124:Immunoenzyme Techniques; D030361:Papillomavirus Infections / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology; D014599:Uterus / Q000378:metabolism / Q000473:pathology*; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000378:metabolism / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004279:DNA, Viral