The expressions of the Rb pathway in cervical intraepithelial neoplasia; predictive and prognostic significance

Gynecol Oncol. 2007 Jan;104(1):207-11. doi: 10.1016/j.ygyno.2006.07.043. Epub 2006 Oct 13.


Objectives: The aim of the study was to assess the expression of the Rb pathway (p16(INK4a)-cdk4-pRb) in cervical intraepithelial neoplasia as a prognostic marker by investigating the association between expression of Rb pathway and the recurrence.

Methods: The study group comprised of 265 paraffin-embedded tissues of the uterine cervix collected from patients between 2001 and 2003. Patients underwent ablative or excisional treatment and were followed for 2 years. RB pathway expression was examined using immunohistochemistry applied to a tissue microarray. HPV detection and genotyping were performed with HPV DNA Chip. Statistical analysis was done by ANOVA test, Student's t test, and Pearson's correlation test.

Results: With increasing CIN grade, p16(INK4a) and cdk4 expression rates increased, while the pRb expression rate decreased. The expression rate of p16(INK4a) was higher (33%) in CIN I with high-risk HPV infection than in CIN I without high-risk HPV infection (19%). The mean expression rates of p16(INK4a) were 29%, 39%, and 64%, respectively, in CIN I, II, and III without recurrence, but 25%, 28%, and 44% in those with recurrence. The mean expression rates of pRb were 47%, 40%, and 18% in CIN I, II, and III without recurrence, respectively, but 48%, 45%, and 34% in those with recurrence.

Conclusion: A relatively low expression rate of p16(INK4a) has prognostic significance for predicting recurrence. The clinical utility of p16(INK4a) status for stratifying patients according to their need for aggressive treatment requires further investigation.

MeSH terms

  • Alphapapillomavirus / classification
  • Alphapapillomavirus / isolation & purification
  • Cervical Intraepithelial Neoplasia / metabolism*
  • Cervical Intraepithelial Neoplasia / pathology
  • Cervical Intraepithelial Neoplasia / virology
  • Cyclin-Dependent Kinase 4 / biosynthesis
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / biosynthesis
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Papillomavirus Infections / complications
  • Papillomavirus Infections / metabolism
  • Paraffin Embedding
  • Predictive Value of Tests
  • Prognosis
  • Retinoblastoma Protein / biosynthesis*
  • Retinoblastoma Protein / metabolism
  • Uterine Cervical Neoplasms / metabolism*
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / virology


  • Cyclin-Dependent Kinase Inhibitor p16
  • Retinoblastoma Protein
  • Cyclin-Dependent Kinase 4