Value of p16^INK4aand Ki-67 immunohistochemical staining in cervical intraepithelial neoplasia grade 2 biopsies as biomarkers for cervical intraepithelial neoplasia grade 3 in cone results

© Science Printers and Publishers, Inc. OBJECTIVE: To evaluate the usefulness of p16INK4a(p16) and Ki-67 staining in high-grade cervical intraepithelial neoplasia (CIN2) biopsies in order to predict CIN3 results in cone specimens, thereby sparing those not likely at risk for CIN3 from unnecessary cone excision. STUDY DESIGN: We retrospectively recruited patients with CIN2 colposcopy-directed biopsy treated by loop electrosurgical excision procedure. The expression of p16 and Ki-67 was qualitatively and quantitatively analyzed in all biopsies and cone specimens. RESULTS: A total of 123 patients from January 2009 to December 2010 were included in the study. CIN3 incone specimens was observed in 35 patients (28.5%). Ki-67 positive immunostaining in >50% of epithelial cells was related to CIN3 diagnoses in cone specimens (p=0.043). However, p16+ and Ki-67+ evaluated by thirds of the epithelial thickness in CIN2 biopsies did not show a significant correlation with the cone results. In multivariate analysis, Ki-67 cell expression over 50% in CIN2 biopsies and high-grade squamous intraepithelial lesion (HSIL) in the previous cytology were statistically associated with CIN3 results in the cone (odds ratio [OR] 2.55, 95% confidence interval [CI] 1.04-6.29; OR 2.68, 95% CI 1.07-6.72, respectively). CONCLUSION: Patients with HSIL in the previous cytology and Ki-67 cell expression over 50% in their CIN2 biopsies could be considered in need of treatment by cone for their higher risk of underlying CIN3 lesions.