Promoter methylation of APC genes in cervical cancer: correlation with clinicopathologic characteristics / 中国癌症杂志

ABSTRACT

Background and purpose: The Writ cell-signaling pathway is the key cellular developmental pathway. Dysregulation of this pathway has been implicated in the initiation and progression of cancer. Adenomatous polyposis coli (APC) is an important tumor suppressor gene of the Writ signaling pathway. The methylation of APC promoter and the accompanying loss of the APC transcript have been shown to occur in a significant proportion of cancers. However, there are few reports on the relationship between cervical cancer and methylation of APC. This study was aimed to investigate the promoter methylation status of the APC genes in cervical cancer and its correlation between clinicopathologic characteristics and the infection of high-risk HPV DNA. Methods: Promoter methylation was evaluated using a MSP (methylation-specific polymerase chain reaction) in 95 cervical cancer tissue specimens and 20 normal controls. The relationship between clinicopathologic parameters and the methylation status was evaluated. Results: The frequencies of promoter methylation of APC in cervical cancer were 56.8%. Cervical cancer had significant higher methylation frequencies than that of the controls (10%, P<0.01). The result showed that the methylation analysis of APC promoter and high-risk HPV DNA testing had good consistency (Kappa=0.348, P<0.001). The promoter methylation of APC was significantly higher in adenocarcinoma (AC) than in squamous cell carcinoma (SCC) (74.1% vs 50.0%, respectively, P<0.05). The larger tumor size, positive lymph node metastasis and positive HPV DNA exhibited an increased promoter methylation frequency for APC (P<0.05). There were no significant associations between the methylation frequencies for APC gene to age, invasion depth, FIGO stage and histological grade. Conclusion: Our results suggested that the promoter methyiation of APC and high-risk HPV DNA testing had good consistency. APC gene promoter methylation was a frequent epigenetic event in cervical carcinoma and had a significant correlation with cancer pathological types.