title: The association between p16 and Ki-67 immunohistostaining and the progression of cervical intraepithelial neoplasia grade 2.
abstract: OBJECTIVE
  To compare the frequency of p16- and Ki-67-positive cells on immunohistostaining among women with progression, persistence, or regression of cervical intraepithelial neoplasia grade 2 (CIN2).
  
  
  METHODS
  A retrospective study was conducted of women with CIN2 diagnosed by histology who were treated at a university hospital in Japan during 2004-2011. The immunostaining patterns for p16 and Ki-67 were analyzed and compared between patients with disease progression, persistence, or regression. Kaplan-Meier analysis was used to evaluate the progression rates stratified by immunostaining, and multivariate analysis of risk factors for progression was performed using the Cox proportional hazards model.
  
  
  RESULTS
  The analysis included 59 women with progression, 35 women with persistence, and 28 women with regression. Deep p16 expression (staining in more than half of the cervical intraepithelial compartment) and positive Ki-67 staining in more than 50% of cells were significantly more common among women with progression than among those with regression. The risk factors for progression of CIN2 were deep p16 expression (P<0.001) and a Ki-67 ratio of more than 50% (P<0.001).
  
  
  CONCLUSIONS
  Among women with CIN2, positive immunohistostaining for p16 and Ki-67 was strongly associated with disease progression.
authors.affiliation: Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan. Electronic address: shingo_m@med.showa-u.ac.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Miyamoto
authors.affiliation: Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Hasegawa
authors.affiliation: Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Morioka
authors.affiliation: Division of Diagnostic Pathology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hirota
authors.affiliation: Division of Diagnostic Pathology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Kushima
authors.affiliation: Department of Obstetrics and Gynecology, Showa University School of Medicine, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Sekizawa
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007564:Japan; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis*; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen
keywords: Cervical intraepithelial neoplasia; Grade 2; Immunohistostaining; Ki-67; p16