Browse > Article
http://dx.doi.org/10.7314/APJCP.2014.15.18.7971

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

Chujan, Suthipong (Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University)
Kitkumthorn, Nakarin (Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Mahidol University)
Siriangkul, Sumalee (Department of Pathology, Faculty of Medicine, Chiangmai University)
Mutirangura, Apiwat (Center of Excellence in Molecular Genetics of Cancer and Human Diseases, Department of Anatomy, Faculty of Medicine, Chulalongkorn University)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.15, no.18, 2014 , pp. 7971-7975 More about this Journal
Abstract
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.
Keywords
CCNA1 promoter methylation; cervical cancer; HPV; duplex MS-PCR; Pap smear;
Citations & Related Records
Times Cited By KSCI : 3  (Citation Analysis)
연도 인용수 순위
1 Bulkmans NW, Berkhof J, Rozendaal L, et al (2007). Human papillomavirus DNA testing for the detection of cervical intraepithelial neoplasia grade 3 and cancer: 5-year followup of a randomised controlled implementation trial. Lancet, 370, 1764-72.   DOI   ScienceOn
2 Bhatla N, Moda N (2009). The clinical utility of HPV DNA testing in cervical cancer screening strategies. Indian J Med Res, 130, 261-5.
3 Castle PE, Fetterman B, Poitras N, et al (2009). Five-year experience of human papillomavirus DNA and Papanicolaou test cotesting. Obstet Gynecol, 113, 595-600.   DOI
4 Chung CH, Gillison ML (2009). Human papillomavirus in head and neck cancer: its role in pathogenesis and clinical implications. Clin Cancer Res, 15, 6758-62.   DOI   ScienceOn
5 de Sanjose S, Diaz M, Castellsague X, et al (2007). Worldwide prevalence and genotype distribution of cervical human papillomavirus DNA in women with normal cytology: a meta-analysis. Lancet Infect Dis, 7, 453-9.   DOI   ScienceOn
6 Eide ML, Debaque H (2012). HPV detection methods and genotyping techniques in screening for cervical cancer. Ann Pathol, 32, 401-9.   DOI
7 GLOBOCAN (2012). Estimated cancer incidence, mortality and prevalence worldwide in 2012.
8 Hansel A, Steinbach D, Greinke C, et al (2014). A promising DNA methylation signature for the triage of high-risk human papillomavirus DNA-positive women. PLoS One, 9, 91905.   DOI
9 Lu Q, Ma D, Zhao S (2012). DNA methylation changes in cervical cancers. Methods Mol Biol, 863, 155-76.   DOI
10 Hesselink AT, Heideman DA, Steenbergen RD, et al (2014). Methylation marker analysis of self-sampled cervico-vaginal lavage specimens to triage high-risk HPV-positive women for colposcopy. Int J Cancer, 135, 880-6.   DOI
11 Junyangdikul P, Tanchotsrinon W, Chansaenroj J, et al (2013). Clinical prediction based on HPV DNA testing by hybrid capture 2 (HC2) in combination with liquid-based cytology (LBC). Asian Pac J Cancer Prev, 14, 903-7.   과학기술학회마을   DOI
12 Muller-Tidow C, Ji P, Diederichs S, et al (2004). The cyclin A1-CDK2 complex regulates DNA double-strand break repair. Mol Cell Biol, 24, 8917-28.   DOI
13 Kitkumthorn N, Yanatatsanajit P, Kiatpongsan S, et al (2006). Cyclin A1 promoter hypermethylation in human papillomavirus-associated cervical cancer. BMC Cancer, 6, 55.   DOI
14 Lui R (2013). Clinical utility of HPV testing. Clin Obstet Gynecol, 56, 17-24.   DOI
15 Mayrand MH, Duarte-Franco E, Coutlee F, et al (2006). Randomized controlled trial of human papillomavirus testing versus Pap cytology in the primary screening for cervical cancer precursors: design, methods and preliminary accrual results of the Canadian cervical cancer screening trial (CCCaST). Int J Cancer, 119, 615-23.   DOI   ScienceOn
16 O'Meara AT (2002). Present standards for cervical cancer screening. Curr Opin Oncol, 14, 505-11.   DOI
17 Priebe AM (2013). 2012 cervical cancer screening guidelines and the future role of HPV testing. Clin Obstet Gynecol, 56, 44-50.   DOI
18 Rai AK, Das D, Kataki AC, et al (2014). Hybrid capture 2 assay based evaluation of high-risk HPV status in healthy women of north-east India. Asian Pac J Cancer Prev, 15, 861-5.   과학기술학회마을   DOI
19 Ronco G, Giorgi-Rossi P, Carozzi F, et al (2006). Human papillomavirus testing and liquid-based cytology in primary screening of women younger than 35 years: results at recruitment for a randomised controlled trial. Lancet Oncol, 7, 547-55.   DOI
20 Rijkaart DC, Berkhof J, Rozendaal L, et al (2012a). Human papillomavirus testing for the detection of high-grade cervical intraepithelial neoplasia and cancer: final results of the POBASCAM randomised controlled trial. Lancet Oncol, 13, 78-88.   DOI   ScienceOn
21 Rijkaart DC, Berkhof J, van Kemenade FJ, et al (2012b). Evaluation of 14 triage strategies for HPV DNA-positive women in population-based cervical screening. Int J Cancer, 130, 602-10.   DOI
22 Ronco G, Giorgi-Rossi P, Carozzi F, et al (2008). Results at recruitment from a randomized controlled trial comparing human papillomavirus testing alone with conventional cytology as the primary cervical cancer screening test. J Natl Cancer Inst, 100, 492-501.   DOI
23 Sarkar S, Horn G, Moulton K, et al (2013). Cancer development, progression, and therapy: an epigenetic overview. Int J Mol Sci, 14, 21087-113.   DOI
24 Saslow D, Solomon D, Lawson HW, et al (2012). American Cancer Society, American Society for Colposcopy and Cervical Pathology, and American Society for Clinical Pathology screening guidelines for the prevention and early detection of cervical cancer. Am J Clin Pathol, 137, 516-42.   DOI   ScienceOn
25 Snijders PJ, Steenbergen RD, Heideman DA, et al (2006). HPVmediated cervical carcinogenesis: concepts and clinical implications. J Pathol, 208, 152-64.   DOI
26 Snijders PJ, Verhoef VM, Arbyn M, et al (2013). High-risk HPV testing on self-sampled versus clinician-collected specimens:a review on the clinical accuracy and impact on population attendance in cervical cancer screening. Int J Cancer, 132, 2223-36.   DOI
27 Tokumaru Y, Yamashita K, Osada M, et al (2004). Inverse correlation between cyclin A1 hypermethylation and p53 mutation in head and neck cancer identified by reversal of epigenetic silencing. Cancer Res, 64, 5982-7.   DOI
28 Wentzensen N, Schwartz L, Zuna RE, et al (2012). Performance of p16/Ki-67 immunostaining to detect cervical cancer precursors in a colposcopy referral population. Clin Cancer Res, 18, 4154-62.   DOI
29 Verhoef VM, Bosgraaf RP, van Kemenade FJ, et al (2014). Triage by methylation-marker testing versus cytology in women who test HPV-positive on self-collected cervicovaginal specimens (PROHTECT-3): a randomised controlled noninferiority trial. Lancet Oncol, 15, 315-22.   DOI
30 Wang ZM (2014). PAX1 methylation analysis by MS-HRM is useful in triage of high-grade squamous intraepithelial lesions. Asian Pac J Cancer Prev, 15, 891-4.   과학기술학회마을   DOI
31 Yanatatsaneejit P, Chalermchai T, Kerekhanjanarong V, et al (2008). Promoter hypermethylation of CCNA1, RARRES1, and HRASLS3 in nasopharyngeal carcinoma. Oral Oncol, 44, 400-6.   DOI
32 Yanatatsaneejit P, Mutirangura A, Kitkumthorn N (2011). Human papillomavirus's physical state and cyclin A1 promoter methylation in cervical cancer. Int J Gynecol Cancer, 21, 902-6.   DOI
33 Yang N, Eijsink JJ, Lendvai A, et al (2009). Methylation markers for CCNA1 and C13ORF18 are strongly associated with high-grade cervical intraepithelial neoplasia and cervical cancer in cervical scrapings. Cancer Epidemiol Biomarkers Prev, 18, 3000-7.   DOI