CCNA1 Promoter Methylation: a Potential Marker for Grading Papanicolaou Smear Cervical Squamous Intraepithelial Lesions

被引:21
作者
Chujan, Suthipong [1 ]
Kitkumthorn, Nakarin [2 ]
Siriangkul, Sumalee [3 ]
Mutirangura, Apiwat [1 ]
机构
[1] Chulalongkorn Univ, Fac Med, Ctr Excellence Mol Genet Canc & Human Dis, Dept Anat, Bangkok 10330, Thailand
[2] Mahidol Univ, Fac Dent, Dept Oral & Maxillofacial Pathol, Bangkok 10700, Thailand
[3] Chiang Mai Univ, Fac Med, Dept Pathol, Chiangmai, Thailand
关键词
CCNA1 promoter methylation; cervical cancer; HPV; duplex MS-PCR; Pap smear; HUMAN-PAPILLOMAVIRUS DNA; RANDOMIZED CONTROLLED-TRIAL; LIQUID-BASED CYTOLOGY; SCREENING GUIDELINES; CANCER PRECURSORS; CLINICAL UTILITY; WOMEN; HYPERMETHYLATION; NEOPLASIA; RECRUITMENT;
D O I
10.7314/APJCP.2014.15.18.7971
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: From our previous study, we established that cyclin A1 (CCNA1) promoter methylation is strongly correlated with multistep progression of HPV-associated cervical cancer, suggesting potential use as a diagnostic maker of disease. Objectives: The purpose of the present study was to assess the prevalence of CCNA1 promoter methylation in residual cervical cells isolated from liquid-based cytology that underwent hrHPV DNA screening for cervical cancer, and then to evaluate this marker for diagnostic accuracy using parameters like sensitivity, specificity, predictive values and likelihood ratio. Methods: In this retrospective study, histopathology was used as the gold standard method with specimens separated into the following groups: negative (n=31), low-grade squamous intraepithelial lesions (LSIL, n=34) and high-grade squamous intraepithelial lesions or worse (HSIL+, n=32). The hrHPV was detected by Hybrid Capture 2 (HC2) and CCNA1 promoter methylation was examined by CCNA1 duplex methylation specific PCR. Results: The results showed the frequencies of CCNA1 promoter methylation were 0%, 5.88% and 83.33%, while the percentages of hrHPV were 66.67%, 82.35% and 100% in the negative, LSIL and HSIL+ groups, respectively. Although hrHPV infection showed high frequency in all three groups, it could not differentiate between the different groups and grades of precancerous lesions. In contrast, CCNA1 promoter methylation clearly distinguished between negative/LSIL and HSIL+, with high levels of all statistic parameters. Conclusion: CCNA1 promoter methylation is a potential marker for distinguishing between histologic negative/LSIL and HSIL+ using cervical cytology samples.
引用
收藏
页码:7971 / 7975
页数:5
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