Tumors of female reproductive systemTumors of female reproductive systemОпухоли женской репродуктивной системы1994-40981999-8627Publishing House ABV Press55210.17650/1994-4098-2017-13-3-63-72GYNECOLOGY. ORIGINAL REPORTSГИНЕКОЛОГИЯ. ОРИГИНАЛЬНЫЕ СТАТЬИEVALUATION OF EXPRESSION OF 4 MIRNAS IN CYTOLOGICAL SAMPLES AS AN ADDITIONAL METHOD OF CERVICAL CANCER DIAGNOSISОЦЕНКА ЭКСПРЕССИИ 4 микроРНК В ЦИТОЛОГИЧЕСКИХ ПРЕПАРАТАХ В КАЧЕСТВЕ ДОПОЛНИТЕЛЬНОГО МЕТОДА ДИАГНОСТИКИ РАКА ШЕЙКИ МАТКИArkhangelskayaP. A.АрхангельскаяП. А.
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Роман Борисович Самсонов.

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KnyazevaM. S.КнязеваМ. С.
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Russian Federation

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Russian Federation

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MalekA. V.МалекА. В.
Russian Federation

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197758 Санкт-Петербург, пос. Песочный, ул. Ленинградская, 68; 143026 Москва, территория инновационного центра «Сколково», ул. Луговая, 4, стр. 9, пом. 16

N.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава РоссииNorth-Western State Medical University named after I. I. Mechnikov, Ministry of Health of RussiaФГБОУ ВО «Cеверо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава РоссииOncosystemООО «Онкосистема»Institute of Molecular and Cellular Biology of the Siberian Branch of the Russian Academy of SciencesФГБУН «Институт молекулярной и клеточной биологии» СО РАНVector-Best LtdАО «Вектор-Бест»Institute of Molecular and Cellular Biology of the Siberian Branch of the Russian Academy of SciencesФГБУН «Институт молекулярной и клеточной биологии» СО РАНN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaNorth-Western State Medical University named after I. I. Mechnikov, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава РоссииФГБОУ ВО «Cеверо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава РоссииN.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава РоссииNational Centre of Clinical and Morphological DiagnosticsООО «Национальный центр клинической морфологической диагностики»N.N. Petrov National Medical Research Oncology Center, Ministry of Health of RussiaOncosystemФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава РоссииООО «Онкосистема»0609201713363720709201707092017https://ojrs.abvpress.ru/ojrs/article/view/552

Introduction. Cervical cancer is the 4th most common cancer among women. The main screening method for cervical cancer is cytological examination of the cervical epithelium. This method allows to evaluate the level of cervical dysplasia (malignant potential) but it has several limitations and flaws. Development and implementation of new methods of molecular and genetic analysis in clinical practice can increase informational value of the traditional cytological examination and therefore objectivity in choosing treatment options.

Objective is to develop and verify a new method of differential diagnosis of severe intraepithelial dysplasia and invasive cervical cancer.

Materials and methods. The method is based on analysis of small non-coding RNA molecules (miRNAs) extracted from the material of traditional Pap smears. Based on literature search, 18 “marker” microRNA molecules were chosen and their expression levels were estimated in 166 samples of Pap smears from cervical canals with different cytological diagnoses. The analysis was performed using reverse transcription polymerase chain reaction.

Results. Estimation of ratios between expression levels of miRNA pairs: 126/375; 20а/375; 126/145 allows to differentiate with high confidence borderline states of severe intraepithelial dysplasia and invasive cervical carcinoma (coefficients of quantitative interpretation of the error curve were 0.8, 0.75, 0.72, respectively).

Conclusions. Analysis of miRNAs in Pap smear samples is a promising additional method of cervical cancer diagnosis. The method is objective and can be proposed as a supporting technique in cases when cytological examination doesn’t allow to differentiate between borderline pathological states of the cervical epithelium. Implementation of the method in clinical practice requires methodological optimization and additional validation using more clinical material.

Введение. Рак шейки матки (РШМ) занимает 4-е место в структуре женской онкологической заболеваемости. Основным методом скрининга РШМ остается цитологическое исследование цервикального эпителия. Этот метод позволяет оценить степень цервикальной дисплазии (потенциал малигнизации), однако он имеет ряд ограничений и недостатков. Разработка и внедрение в клиническую практику новых методов молекулярно-генетического анализа может повысить информативность традиционного цитологического исследования и, следовательно, объективность выбора лечебной тактики.

Цель исследования – разработка и апробация нового метода дифференциальной диагностики тяжелой внутриэпителиальной дисплазии и инвазивной карциномы шейки матки.

Материалы и методы. Метод основан на анализе малых некодирующих молекул РНК (микроРНК), изолированных из материала традиционных цитологических мазков. По результатам исследования литературных данных выбраны 18 «маркерных» молекул микроРНК, уровень экспрессии которых оценен в 166 препаратах мазков из цервикального канала с различными цитологическими диагнозами. Анализ проведен методом обратной транскрипции с последующей полимеразной цепной реакцией.

Результаты. Оценка соотношения экспрессионной активности пар микроРНК: 126/375; 20а/375; 126/145 позволяет дифференцировать пограничные состояния тяжелой внитриэпителиальной дисплазии и инвазивной карциномы шейки матки с высокой достоверностью (показатели количественной интерпретации кривой ошибок: 0,8; 0,75; 0,72 соответственно).

Выводы. Анализ микроРНК в препаратах цитологических мазков представляется перспективным методом дополнительной диагностики РШМ. Метод является объективным и может быть предложен в качестве вспомогательного в случаях, когда цитологическое исследование не позволяет уверенно дифференцировать пограничные патологические состояния цервикального эпителия. Внедрение метода в клиническую практику требует методологической оптимизации и дополнительной валидации на большем клиническом материале.

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