Hyperemethylation of p16^INK4a is associated with cervical neoplasia

B135

Objective: Epigenetic mechanisms such as DNA methylation play an important role in the development of cervical preinvasive lesion and invasive cancer. The aim of this study is to examine the methylation status of p16^INK4a in carcinoma in situ (CIS) and invasive squamous cell carcinoma of uterine cervix and the correlation between methylation status and disease progression.
 Methods: The present study included 59 patients in all, 7 non-cancer controls, 21 patients with CIS, and 31 patients with invasive squamous cell carcinoma (Ia 6, Ib 15, IIa 6, IIb 3, and IVb 1 patient). Cervical tissues were obtained from cone biopsy specimen or hysterectomy specimen. Tumor tissues were selectively microdissected. DNA was isolated using DNA isolation kit. Methylation status of p16^INK4a gene was analyzed by methylation-specific PCR (MSP) using primer, p16 M1. Comparison of each variable were performed using the χ² test or Fisher's extract test.
 Results: Of the 52 cervical neoplaisa investigated, 29 (55.8%) tumors showed methylation. The methylation rate for CIS and invasive SCC was 57.1% (12/21) and 54.8% (17/31), respectively compared to 14.2%(1/7) in control group. The incidence of methylation was higher in cervical neoplasia group with borderline significance (p=0.052). There was no association of methylation status of p16^INK4a with clinicopathologic parameters of cervical cancer such as age, clinical stage, tumor size, lymph node metastasis or parametrial invasion.
 Conclusion: Hypermethylation of the p16^INK4 is frequently observed in preinvasive or invasive squamous cell carcinoma of cervix. However no association was observed between methylation status of p16^INK4 and clinicopathologic parameters of cervical cancer. Further study with a larger number of cases is in need to confirm these data.