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.

Bioptická Laboratoř s r o Pilsen Czech Republic

Cytopathos s r o Bratislava Slovak Republic

Department of Obstetrics and Gynecology Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic

Department of Pathology Medical Faculty Charles University Hospital Pilsen Charles University Pilsen Czech Republic

Department of Pathology Royal Columbian Hospital University of British Columbia Vancouver British Columbia Canada

Department of Pathology Slovak Medical University Bratislava Slovak Republic

Institute of Biostatistics and Analyses Faculty of Medicine Masaryk University Brno Czech Republic

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The Methylation Test Is Highly Sensitive for HPV-Associated Endocervical Adenocarcinoma and Could Be Helpful as a Cytological Ancillary Test in Women With a PAP-Smear Diagnosis of Severe Glandular Lesion (AGC-NEO+)