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: Satoru Ozaki, Yoh Zen, Masaki Inoue
• Journal: Human pathology (Hum Pathol) Vol. 42 Issue 7 Pg. 1007-12 (Jul 2011) ISSN: 1532-8392 [Electronic] United States
• PMID: 21315414 (Publication Type: Journal Article)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Cell Cycle Proteins
• Cyclin-Dependent Kinase Inhibitor p16

Topics

• Adult
• Biomarkers, Tumor (metabolism)
• Cell Cycle Proteins (metabolism)
• Cyclin-Dependent Kinase Inhibitor p16 (metabolism)
• Disease Progression
• Female
• Humans
• Immunohistochemistry
• Middle Aged
• Papillomavirus Infections (pathology)
• Predictive Value of Tests
• Prognosis
• Statistics, Nonparametric
• Uterine Cervical Neoplasms (diagnosis, pathology, virology)
• Uterine Cervical Dysplasia (diagnosis, pathology, virology)