The detection of DNA methylation of tumour suppressor genes in cervical high-grade squamous intraepithelial lesion: A prospective cytological-histological correlation study of 70 cases

ONDIČ, Ondrej, Jana NĚMCOVÁ, Reza ALAGHEHBANDAN, Kateřina ČERNÁ, Barbora GOMOLČÁKOVÁ, Iva KINKOROVÁ-LUŇÁČKOVÁ, Jan CHYTRA, Henrieta ŠIDLOVÁ, Ondřej MÁJEK and Jiří BOUDA. The detection of DNA methylation of tumour suppressor genes in cervical high-grade squamous intraepithelial lesion: A prospective cytological-histological correlation study of 70 cases. CYTOPATHOLOGY. HOBOKEN: WILEY, 2019, vol. 30, No 4, p. 426-431. ISSN 0956-5507. Available from: https://dx.doi.org/10.1111/cyt.12718.

Basic information

• Original name: The detection of DNA methylation of tumour suppressor genes in cervical high-grade squamous intraepithelial lesion: A prospective cytological-histological correlation study of 70 cases
• Authors: ONDIČ, Ondrej (203 Czech Republic, guarantor), Jana NĚMCOVÁ (203 Czech Republic), Reza ALAGHEHBANDAN (124 Canada), Kateřina ČERNÁ (203 Czech Republic), Barbora GOMOLČÁKOVÁ (203 Czech Republic), Iva KINKOROVÁ-LUŇÁČKOVÁ (203 Czech Republic), Jan CHYTRA (203 Czech Republic), Henrieta ŠIDLOVÁ (703 Slovakia), Ondřej MÁJEK (203 Czech Republic, belonging to the institution) and Jiří BOUDA (203 Czech Republic).
• Edition: CYTOPATHOLOGY, HOBOKEN, WILEY, 2019, 0956-5507.

Other information

• Original language: English
• Type of outcome: Article in a journal
• Field of Study: 10601 Cell biology
• Country of publisher: United States of America
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Impact factor: Impact factor: 1.493
• RIV identification code: RIV/00216224:14110/19:00110577
• Organization unit: Faculty of Medicine
• Doi: http://dx.doi.org/10.1111/cyt.12718
• UT WoS: 000472237900011
• Keywords in English: cervix; cytology; HSIL; hypermethylation; methylation
• Tags: 14119612, rivok
• Tags: International impact, Reviewed

Abstract

Background DNA methylation has been suggested as one of the epigenetic changes promoting carcinogenesis. The aim of this study was to prospectively evaluate the methylation status of CADM 1, MAL and hsa-miR-124 genes in high-grade squamous intraepithelial lesion (HSIL) liquid-based cytology (LBC) samples with a histological correlation. Methods Seventy histologically confirmed cases of HSIL paired with prior screening LBC diagnosis of HSIL within a 3-month interval were selected. Histologically, the lesions were reviewed and assessed including: (a) number of blocks harbouring dysplastic squamous epithelium; (b) number of blocks containing glandular extension of dysplastic epithelium; and (c) the depth of glandular extension (which was assessed semi-quantitatively as graded 1-3). Human papillomavirus (HPV) subtyping was performed from residual LBC materials using the LINEAR ARRAY HPV Genotyping Test and in-house polymerase chain reaction targeting the HPV E1 gene. The detection of methylation silencing of tumour suppressor genes CADM1, MAL and hsa-miR-124 was performed by multiplex methylation-specific real-time polymerase chain reaction. Results A positive methylation status was detected in 41 cases (58.6%). The number of blocks with HSIL varied from one to 13. Glandular extension was seen in 44 cases with the number of blocks involved ranging from one to 10. The depth of HSIL glandular extension varied. Conclusion The DNA methylation test allows HSIL lesions to be divided into two distinct groups of methylated HSIL in significantly older patients and unmethylated HSIL in younger patients. This study was not able to prove that methylation status in cervical HSIL correlates with the size of the lesion (measured by the number of blocks involved) or with HSIL propensity for endocervical glandular extension, nor with HPV type or multi-infection.