Application of molecular genetic methods for the diagnosis and prediction of severe dysplasia and cervical cancer


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Abstract

Materials and methods: The study included 466 patients of Outpatient Department of the Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of Russia. Cytological examination, HPVtesting, colposcopy, cervical biopsy (when indicated), histological examination, and gene- expression analysis in real-time RT-PCR for mRNA expression profile of 11 genes were performed. 90 patients with "minor" forms of cervical intraepithelial neoplasia underwent dynamic observation every 6 months within 24 months. Results: A method for detection of severe dysplasia, cervical cancer and the risk of progression of "minor" forms of HPV-associated diseases was developed. Using regression analysis of MKI67, CDKN2A, CCNB1, MYBL2, EXO, ANLN, UBE2T, PGR, ESR1, BAG1, BCL2 mRNA expression and considering high oncogenic risk of HPV, an algorithm for calculation of the risk index (RI) of cervical lesions was proposed. 88.3% of HSIL and 100% of CC cases were detected using the RI. For "minor" cervical lesions, unfavorable and favorable prognosis were confirmed in 81.5% and in 84.1% of cases, respectively. Conclusion: The developed model can be prospectively applied in clinical practice for screening and prevention of cervical cancer as an additional testfor sorting the samples with "severe" lesions and assessment of the risk of the disease progression, as well as selecting the patients for colposcopy and biopsy according to indications.

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About the authors

Olga V. Burmenskaya

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: o_bourmenskaya@oparina4.ru
Dr. Sci. (Bio), Head of the Laboratory of Oncological Genetics

Niso M. Nazarova

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: grab2@yandex.ru
Dr. Med. Sci., Senior Researcher

Elena G. Sycheva

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: el.bona@mail.ru
PhD, doctor

Vera N. Prilepskaya

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Dr. Med. Sci., Professor

Dmitry Yu. Trofimov

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Dr. Sci. (Bio), Professor, Director of the Institute of Reproductive Genetics

Gennady T. Sukhikh

Academician V.I. Kulakov National Medical Research Center for Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia

Email: g_sukhikh@oparina4.ru
Academician RAS, Professor, Director

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