P12-08METHYLATION OF INHIBITORS WNT SIGNALLING PATHWAY AND HPV TYPES IN CERVICAL CANCER

12. Molecular markers
K.D. Segati 1, V.A. Saddi 2, R. Figueiredo-Alves 3, K.P. Almeida-Carvalho 1, L. Termini 4, W. D’alessandro 5, M.A. Carneiro 1, E. Boccardo 6, L.C. Zeferino 7, S.H. Rabelo-Santos 5.
1Institute of Tropical Pathology and Public Health, Federal University of Goiás; Goiânia, GO, Brazil. (Brazil), 2Program in Environmental Sciences and Health, Pontifical Catholic University of Goiás; Laboratory of Oncogenetics and Radiology, Associação de Combate ao Câncer; Goiânia, GO, Brazil. (Brazil), 3Department of Obstetrics and Gynecology, School of Medical Sciences, Federal University of Goiás, Goiânia, GO, Brazil. (Brazil), 4Center for Translational Investigation in Oncology, ICESP - Cancer Institute of the State of São Paulo, Teaching Hospital, School of Medicine, University of São Paulo; São Paulo, SP, Brazil. (Brazil), 5School of Pharmacy, Federal University of Goiás; Goiânia, GO, Brazil. (Brazil), 6University of São Paulo; São Paulo, SP, Brazil. (Brazil), 7Department of Obstetrics and Gynecology, State University of Campinas (UNICAMP); Campinas, SP, Brazil. (Brazil)

Background / Objectives

Most cervical cancer is caused by persistent infection with high-risk human papillomavirus (HR-HPV). Genetic and epigenetic changes as the silencing of inhibitors WNT signaling pathway can affect the outcome of HR-HPV infection. Considering that the methylation of DNA is important for the carcinogenic process, the aim of this study was to analyze status of methylation of DKK3, SOX17 and SFRP2 genes regarding HR-HPV types 16/18/45, staging, degree of differentiation and origin of cervical cancer. 


Methods

A total of 169 paraffin-embedded tissue blocks from biopsies performed in cervical cancer patients were selected. HPV detection and genotyping were performed using the INNO-LiPA HPV Genotyping assay. After treatment with sodium bisulfite, the samples were submitted to MS-PCR


Results

The age of the patients at the time of diagnosis of cervical cancer ranged from 26 to 91 years, with an average of 52.3 years (95% CI = 49.3-54.7). The mean age of the patients who were diagnosed with adenocarcinoma was 46 years (95% CI = 40.7-51.3). Squamous cell carcinoma on average affected 53.9 year old women (95% CI = 49.7-56.2). A total prevalence of HPV was 94.3%. All cases as diagnosed squamous cell carcinoma were positive for HPV among cases of adenocarcinomas, 86.4% were positive for HPV. The methylation of genes was a prevalent event in cervical cancer ranging from 65.5% to 90.0%. The prevalence of HPV 16, 18 and 45 was 82.2%. Infection with HR-HPV showed a significant association for SFRP2 (p=0.05). Methylation of the SOX17 gene was positively associated with lower severity of stages of cervical cancer (p=0.04). The methylation of the SOX17 gene was associated with the presence of well or moderately differentiated tumors (p=0.01). When all genes were considered an association with better differentiation was observed (p=.0.05) In addition, there was a significant association between infection by the HPV 16, 18 and 45 and the diagnosis of adenocarcinoma (p=0.01). A borderline association was observed between the methylation of the DKK3 and SOX17 genes and the diagnosis of adenocarcinoma (p=0.07).


Conclusion

The methylation of inhibitors WNT signaling pathway and HPV 16, 18 and 45 infections are frequent event during multistep carcinogenesis, however, only was significant association with SFRP2 metilation. SOX17 metilation was be related with lower cervical cancer severity but not with HPV types. Adenocarcinomas showed a significant association with HPV 16, 18 and 45 infections, however showed a borderline association with DKK3 and SOX17 metilation. 


References