p16 and Ki-67 immunostaining in atypical immature squamous metaplasia of the uterine cervix: correlation with human papillomavirus detection

Arch Pathol Lab Med. 2007 Sep;131(9):1343-9. doi: 10.5858/2007-131-1343-PAKIIA.

Abstract

Context: Atypical immature squamous metaplasia (AIM) of the cervix is a loosely defined entity characterized by immature metaplastic cells with mild cytologic atypia.

Objective: To examine whether a combination of immunostaining for p16 and Ki-67 could be used to stratify AIM cases into 3 categories: benign, cases with nondiagnostic atypia, and high-grade squamous intraepithelial lesion (HSIL).

Design: The study consisted of 37 cases of AIM, 23 cases of benign cervical mucosa (NEG), and 36 cases of HSIL. All cases were tested for high-risk human papillomaviruses using SPF 10 polymerase chain reaction and immunostained for p16 and Ki-67.

Results: All cases of HSIL were positive for both p16 and Ki-67. All but 2 benign control cases were negative for both p16 and Ki-67. Seven cases of AIM (19%) displayed a pattern of immunostaining identical to HSIL, and these most likely represent a spectrum of HSIL. A total of 54% of cases of AIM were negative for both p16 and Ki-67, consistent with benign reactive atypia. Two AIM cases (5%) were negative for p16 and positive for Ki-67 in the area adjacent to an ulcer, representing regeneration. Finally, 22% of AIM cases were positive for p16 and negative for Ki-67; such cases may represent a precursor of HSIL or, alternatively, a regressing HSIL.

Conclusion: The combination of immunostaining for p16 and Ki-67 is helpful in limiting of the number of cases with nondiagnostic atypia of the cervix.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Case-Control Studies
  • Cervix Uteri / metabolism*
  • Cervix Uteri / pathology
  • Cervix Uteri / virology
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Female
  • Humans
  • Ki-67 Antigen / genetics
  • Ki-67 Antigen / metabolism*
  • Metaplasia / classification
  • Metaplasia / diagnosis
  • Metaplasia / metabolism*
  • Metaplasia / virology
  • Middle Aged
  • Mucous Membrane / metabolism
  • Mucous Membrane / pathology
  • Papillomavirus Infections / diagnosis
  • Papillomavirus Infections / metabolism*
  • Papillomavirus Infections / pathology
  • Sensitivity and Specificity
  • Uterine Cervical Dysplasia / diagnosis
  • Uterine Cervical Dysplasia / metabolism
  • Uterine Cervical Dysplasia / pathology
  • Uterine Cervical Neoplasms / diagnosis
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / pathology

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • Ki-67 Antigen