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EP265 The role of methylation silencing of tumor suppressor genes in cervical HSIL: a prospective cytologic-histologic correlation study of 70 cases
  1. O Ondic,
  2. J Bouda,
  3. J Nemcova,
  4. I Kinkorova-Lunackova,
  5. J Chytra,
  6. J Presl,
  7. R Alaghehbandan,
  8. K Cerna,
  9. B Gomolcakova,
  10. J Kostun,
  11. H Sidlova,
  12. P Vlasak and
  13. O Majek
  1. 1Dept of Pathology, Faculty of Medicine and University Hospital in Pilsen, Charles University in Prague
  2. 2Bioptical Laboratory
  3. 3Dept of OBGYN
  4. 4Faculty of Medicine and University Hospital in Pilsen, Charles University in Prague, Plzen, Czech Republic
  5. 5Dept of Pathology, University of British Columbia, Royal Columbian Hospital, Vancouver, BC, Canada
  6. 6Cytopathos, s.r.o., Bratislava
  7. 7Institute of Biostatistics and Analyses, Masaryk University, Brno, Czech Republic

Abstract

Introduction/Background Methylation silencing of tumor suppressor genes has been suggested as one of the epigenetic changes promoting carcinogenesis. The aim of this study was to prospectively evaluate methylation status of CADM 1, MAL, hsa-miR-124 genes in HSIL (high grade squamous intraepithelial lesion) LBC (liquid based cytology) samples with histologic correlation.

Methodology 70 histologically confirmed cases of HSIL paired with prior screening LBC diagnosis of HSIL within 3 months interval were selected. Histologically, the lesions were reviewed and assessed including 1) number of blocks harboring dysplastic squamous epithelium, 2) number of blocks containing glandular extension of dysplastic epithelium, and 3) the depth of glandular extension (which was assessed semi-quantitatively as graded 1-3). From residual LBC materials, HPV subtyping was performed, using LINEAR ARRAY HPV Genotyping Test and in house PCR targeting HPV E1 gene. Detection of methylation silencing of tumor suppressor genes CADM1, MAL, and hsa-miR-124 was performed by multiplex methylation specific real-time PCR.

Results Positive methylation status was detected in 41 cases (58.6%). Number of blocks with HSIL varied from 1 to 13. Glandular extension was seen in 44 cases with number of blocks involved ranging from 1 to 10. The depth of HSIL glandular extension varied.

Conclusion Methylation status in cervical HSIL does not correlate 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.

Disclosure The study was partially supported with grant provided by the Ministry of Health of the Czech Republic - Conceptual Development of Research Organization (Faculty Hospital in Pilsen - FNPl, 00669806). There are no any other financial disclosures from the authors.

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