title: Biomarker expression in cervical intraepithelial neoplasia: potential progression predictive factors for low-grade lesions.
abstract: The aim of this study was to reveal whether 3 biomarkers (p16INK4a, ProEx C, and human papilloma virus DNA) are useful in the diagnosis of cervical intraepithelial neoplasia and whether they could predict disease progression of cervical intraepithelial neoplasia-1. We analyzed 252 cervical specimens: nondysplastic mucosa (n = 9), cervical intraepithelial neoplasia (n = 229), and squamous cell carcinoma (n = 14). Immunostaining for p16INK4a and ProEx C, and the hybridcapture II assay for human papilloma virus DNA were performed. Expression of p16INK4a and staining for ProEx C were significantly higher in intraepithelial neoplasia 2/3 (96%-100%) than in nondysplastic mucosa (11%) or intraepithelial neoplasia 1 (40%-53%). Human papilloma virus DNA was detected in 69% of intraepithelial neoplasia-1, 95% of intraepithelial neoplasia-2, and 100% of intraepithelial neoplasia 3. Of 99 patients with intraepithelial neoplasia 1 for whom follow-up data was available, 62 (73%) showed spontaneous regression, 17 (20%) demonstrated persistent low-grade lesion, and 7 (7%) progressed to intraepithelial neoplasia 2/3. Expressions of p16INK4a and staining with ProEx C were significantly higher in the progression group than in the regression group. Testing for p16INK4a and ProEx C was sensitive (86%) and moderately specific (60% and 61%, respectively) in predicting the progression of cervical intraepithelial neoplasia 1. Human papilloma virus DNA testing was highly sensitive (100%) but less specific (37%). In conclusion, this study revealed that p16INK4a and ProEx C are useful biomarkers for the diagnosis of cervical intraepithelial neoplasia, and have potential as predictors of progression of low-grade lesions.
authors.affiliation: Division of Pathology, Kanazawa University Hospital, Kanazawa 920-8641, Japan. s-ozaki@med.kanazawa-u.ac.jp
authors.forename: Satoru
authors.initials: S
authors.lastname: Ozaki
authors.forename: Yoh
authors.initials: Y
authors.lastname: Zen
authors.forename: Masaki
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D030361:Papillomavirus Infections / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D018709:Statistics, Nonparametric; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000473:pathology / Q000821:virology; D002578:Uterine Cervical Dysplasia / Q000175:diagnosis* / Q000473:pathology / Q000821:virology
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019941:Cyclin-Dependent Kinase Inhibitor p16