Potential diagnostic value of P16 expression in premalignant and malignant cervical lesions

Abstract

• BACKGROUND: The goal of this study was to evaluate the results of the expression of p16INK4a in normal uterine cervical epithelium, low-grade cervical intraepithelial neoplasia, (CIN) high-grade CIN, squamous cell carcinoma (SCC), and adenocarcinoma of the cervix, in order to help draw a distinction between low risk and high risk patients with cervical lesions.
• METHODS: P16INK4a expression was evaluated by immunohistochemistry in 78 paraffin-embedded tissue samples including 39 normal cervical tissues, 11 low-grade CINs, 11 high-grade CINs, 22 cervical SCCs and 8 cervical adenocarcinomas. Two parameters in immunohistochemical p16 expression were evaluated: percentage of p16-positive cells, and reaction intensity.
• RESULTS: The p16INK4a expression rate was 81.8% in low-grade CINs, 91% in high-grade CINs, 90% in SCCs and 75% in cervical adenocarcinomas. 10% of normal cervical samples expressed p16. Moreover, there is a significant relationship between the histological diagnoses and percentage of positive cells and reaction intensity of p16 (p < 0.005). The intensity of the reaction is the best parameter to evaluate the positivity of p16.
• CONCLUSIONS: Over-expression of the p16INK4a is typical for dysplastic and neoplastic epithelia of the uterine cervix. However, p16INK4a-negative CINs and carcinomas do exist. Although negative p16INK4a expression does not definitely exclude the patient with cervical lesion from the high-risk group, immunohistochemical study for p16INK4a may be used as a supplementary test for an early diagnosis of cervical cancers.
• KEYWORDS: P16 INK4a, Cervical Intrepithelial Neoplasia, Immunohistochemistry, Human Papilloma Virus