DNA methylation patterns of RAR-ß2 and RASSF1A gene promoters in FNAB samples from Greek population with benign or malignant breast lesions.

BACKGROUND: Promoter hypermethylation is common in Breast Cancer (BC) with studies mainly in histological specimens showing frequent methylation of tumor suppressor genes (TSGs) compared with normal tissues. The aim of this study was to estimate the frequency of promoter methylation of RAR-ß2 and RASSF1A genes in breast FNAB material aiming to evaluate the methylation status of these two genes as biomarker for detecting BC in Greek population. METHODS: FNAB material from 104 patients was collected for cytological evaluation and epigenetic analysis. DNA was extracted and subjected to bisulfite conversion. A methylation-specific PCR was carried out and the final products were separated with electrophoresis in 2% agarose gels. RESULTS: From 104 samples, RASSF1A hypermethylation was observed in 78 (75%) and RAR-ß2 hypermethylation in 64 (61.6%). 84% and 78% of the cases diagnosed with breast malignancy (n = 50) were methylated for RASSF1A and RAR-ß2, respectively. Methylated RASSF1A and RAR-ß2 were also detected in 88.3% and 76.5% in samples diagnosed as suspicious for malignancy (n = 17) and in 57.2% of samples diagnosed with atypia (n = 14). The Odds Ratio for breast malignancy was 4.545 in patients with RASSF1A hypermethylation and 9.167 in patients with RAR-ß2 hypermethylation underlying their promoter's methylation positive correlation with breast malignancy. CONCLUSION: To optimize the sensitivity and specificity of this epigenetic setting, more TSGs related to BC should be gradually imported in our evaluated methylation panel and be validated in a larger study sample with the aim that the obtained epigenetic profiles will provide clinicians with valuable tools for management of BC patients in Greece.

Cervical Pathology Following HPV Vaccination in Greece: A 10-year HeCPA Observational Cohort Study.

BACKGROUND: In Greece the population-level impact of HPV vaccination is unknown due to lack of official registries. This study presents in a pragmatic frame the comparison of cervical pathology data between HPV-vaccinated and unvaccinated women referred for colposcopy. PATIENTS AND METHODS: This is an observational prospective cohort study performed in 7 academic Obstetrics and Gynaecology Departments across Greece between 2009-2019. Cases were women that had completed HPV vaccination before coitarche and were referred for colposcopy due to abnormal cytology. For each vaccinated woman an unvaccinated matched control was selected. RESULTS: A total of 849 women who had been vaccinated before coitarche and 849 unvaccinated controls were recruited. The combination of cytological, colposcopic and molecular findings necessitated treatment in only a single case among vaccinated (0.1%) and in 8.4% among unvaccinated. CONCLUSION: HPV vaccination at a proper age can markedly reduce development of severe cervical precancers and consequently the need for treatment, as well as their long-term related obstetrical morbidity.