title: p16(INK4a) immunohistochemistry is a promising biomarker to predict the outcome of low grade cervical intraepithelial neoplasia: comparison study with HPV genotyping.
abstract: OBJECTIVE
  In cervical intraepithelial neoplasia (CIN), p16(INK4a) immunohistochemistry has been reported to be a useful diagnostic biomarker. However, limited information is available about the association between the p16(INK4a) immunohistochemistry and the outcomes of CIN. Here, we report p16(INK4a) immunohistochemistry as an effective biomarker to predict the outcomes of CIN.
  
  
  METHODS
  p16(INK4a) immunohistochemistry was performed in patients with CIN from January 2000 to August 2009. Among these patients, we have performed a retrospective analysis of the medical records to evaluate the outcome of CIN 1-2 and performed statistical analysis to determine the correlation between p16(INK4a) expression and the outcomes. We also performed HPV genotyping and analyzed the relation between the infecting human papillomavirus (HPV) genotype and the outcomes.
  
  
  RESULTS
  A total of 244 patients, including 82 with CIN 1, 60 with CIN 2, and 102 with CIN 3, were examined. The rate of p16(INK4a) overexpression increased with increasing CIN grade, 20.7% for CIN 1, 80.0% for CIN 2, and 89.2% for CIN 3, with significant differences between CIN 1 and CIN 2-3 group. In the 131 CIN 1-2 patients, the progression rate was significantly higher for the patients showing p16(INK4a) overexpression than for those not showing p16(INK4a) overexpression (p=0.005); the regression rate was also found to be significantly lower for the patients showing p16(INK4a) overexpression (p=0.003). High-risk HPV genotypes were detected in 73 patients (73.7%). Both progression and regression rates were not significantly different between the high-risk HPV-positive and HPV-negative groups (p=0.401 and p=0.381, respectively).
  
  
  CONCLUSIONS
  p16(INK4a) overexpression was correlated with the outcome of CIN 1-2, and p16(INK4a) is considered to be a superior biomarker for predicting the outcome of CIN 1-2 compared with HPV genotyping.
authors.affiliation: Department of Obstetrics and Gynecology, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Sakiko
authors.initials: S
authors.lastname: Nishio
authors.forename: Takuma
authors.initials: T
authors.lastname: Fujii
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nishio
authors.forename: Kaori
authors.initials: K
authors.lastname: Kameyama
authors.forename: Miyuki
authors.initials: M
authors.lastname: Saito
authors.forename: Takashi
authors.initials: T
authors.lastname: Iwata
authors.forename: Kaneyuki
authors.initials: K
authors.lastname: Kubushiro
authors.forename: Daisuke
authors.initials: D
authors.lastname: Aoki
keywords: Biomarker; Cervical intraepithelial neoplasia; Human papillomavirus; Immunohistochemistry; p16INK4a