title: Value of p16(INK4a) and Ki-67 Immunohistochemical Staining in Cervical Intraepithelial Neoplasia Grade 2 Biopsies as Biomarkers for Cervical Intraepithelial Neoplasia Grade 3 in Cone Results.
abstract: OBJECTIVE
  To evaluate the usefulness of p16(INK4a) (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.
  
  
  METHODS
  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 in cone 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).
  
  
  CONCLUSIONS
  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.
authors.forename: Ester
authors.initials: E
authors.lastname: Miralpeix
authors.forename: Josep M
authors.initials: JM
authors.lastname: Solé-Sedeño
authors.forename: Gemma
authors.initials: G
authors.lastname: Mancebo
authors.forename: Belen
authors.initials: B
authors.lastname: Lloveras
authors.forename: Beatriz
authors.initials: B
authors.lastname: Bellosillo
authors.forename: Ramon
authors.initials: R
authors.lastname: Carreras
authors.forename: Francesc
authors.initials: F
authors.lastname: Alameda
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001706:Biopsy; D003127:Colposcopy; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000096:biosynthesis* / Q000235:genetics; D003581:Cytodiagnosis; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D060787:Neoplasm Grading; D027383:Papillomaviridae / Q000472:pathogenicity; D011237:Predictive Value of Tests; D011247:Pregnancy; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16; D019394:Ki-67 Antigen