Cervical intraepithelial neoplasia: Analysis of mRNA profile in the practice of liquid-based cytology
Objective. To assess whether patients with CIN 2+ and CIN1 or less can be differentiated based on the mRNA expression of a 21-gene panel by quantitative PCR in the material of preservative fluid collection vials with CellPrep PAP test samples.Melnikova N.V., Bozhenko V.K., Antonova I.B., Babaeva N.A., Yarovaya N.Yu., Bolotina N.A., Zakharenko M.V., Senchukova A.L., Akopova N.B., Aleksandrova N.V., Burmenskaya O.V., Ashrafyan L.A.
Subjects and methods. The mRNA expression level of 21 genes (Ki-67, STK-15, CCNB1, CCND1, MYC, MYBL2, P16INK4A, PTEN, BIRC5, BCL2, BAG1, TERT, NDRG1, ESR1, PGR, HER2, GRB7, MGB1, MMP11, CTSL2, and CD68) was determined by quantitative PCR in the material of preservative fluid collection vials after CellPrep PAP test in 59 patients who had been treated at the Russian Research Center of Roentgenology and Radiology in 2015-2016. The test of significance was the results of comparison with subsequent histological examination.
Results. Discriminant analysis has established that a combined assessment of ESR1 and MYBL2 mRNA expression levels allows correct classification in 88.24% of cases of CIN2+ changes and in less than 84.0% of cases of histologically confirmed CIN1. The combined assessment of mRNA expression levels of 17 genes (ESR1, MYBL2, CD68, PTEN, CCND1, BCL2, HER2, MMP11, TERT, STK15, P16INK4A, BAG1, CTSL2, KI67, CCNB1, GRB7, and NDRG1) permits differentiation of CIN 2+ and CIN1 or less cases with an accuracy at 98.3%. The coincidence rate of the classification with the data of histological examination was 100.0% for the CIN2+ group and 96.0% for the histologically confirmed CIN1 or less group.
Conclusion. It has been shown for the first time that the mRNA expression of a large group of genes can be analyzed by quantitative PCR in the material of CellPrep liquid-based cytology in the PAP test. Assessment of the expression of a panel of 21 genes, which complements the preoperative morphological diagnosis of precancerous processes and cancer of the cervix uteri in the material of liquid-based cytology, allows a high-precision differential diagnosis of 2 clinically important groups, such as the CIN 2+ and CIN1 or less ones (intact epithelium/benign tissue changes of the cervix).
Keywords
cervical pathology
gene expression
mRNA
liquid-based cytology
cytology
References
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Received 03.02.2017
Accepted 17.02.2017
About the Authors
Melnikova Nadezhda Vasilevna, Ph.D., Leading Researcher of the Laboratory of Immunology, oncocytology and cell therapy in oncology, Russian Research Center of Roentgenology and Radiology, Ministry of Health of Russia. 117997 Russia, Moscow, Profsoyuznaya str. 86. Tel.: +74953339130. E-mail: n_melnikova@list.ruBozhenko Vladimir Konstantinovich, MD, Head of the Department of Molecular Biology and Experimental Tumor Therapy, Russian Research Center of Roentgenology and Radiology, Ministry of Health of Russia. 117997 Russia, Moscow, Profsoyuznaya str. 86. Tel.: +74991201114. E-mail: vbojenko@mail.ru
Antonova Irina Borisovna, MD, Head of the Laboratory of prevention, early diagnostics and combination treatment of cancer diseases, Russian Research Center of Roentgenology and Radiology, Ministry of Health of Russia. 117997 Russia, Moscow, Profsoyuznaya str. 86. Tel.: +74991206077. E-mail: iran24@yandex.ru
Babaeva Nataliya Aleksandrovna, MD, Leading researcher of Laboratory of prevention, early diagnostics and combined treatments of cancer diseases, Russian Research Center of Roentgenology and Radiology, Ministry of Health of Russia. 117997 Russia, Moscow, Profsoyuznaya str. 86. Tel.: +74991206077. E-mail: natbabaeva@yandex.ru
Yarovaya Nataliya Yurevna, Ph.D., Head of the Laboratory of Cytology at the Pathology department, Russian Research Center of Roentgenology and Radiology,
Ministry of Health of Russia. 117997 Russia, Moscow, Profsoyuznaya str. 86. Tel.: +74991201114. E-mail: natalya-yarovaya@yandex.ru
Bolotina Nataliya Aleksandrovna, Ph.D., Pathologist at the Pathology department, Russian Research Center of Roentgenology and Radiology, Ministry of Health of Russia. 117997 Russia, Moscow, Profsoyuznaya str. 86. Tel.: +74953339130. E-mail: soloma-natali@yandex.ru
Zakharenko Margarita Vladimirovna, Junior Researcher of the Laboratory of Immunology, oncocytology and cell therapy in oncology, Russian Research Center of Roentgenology and Radiology, Ministry of Health of Russia. 117997 Russia, Moscow, Profsoyuznaya str. 86. Tel.: +74991201114. E-mail: zak-margarita@mail.ru
Senchukova Anna Leonidovna, Ph.D., Researcher of the Laboratory of Immunology, oncocytology and cell therapy in oncology, Russian Research Center of Roentgenology and Radiology, Ministry of Health of Russia. 117997 Russia, Moscow, Profsoyuznaya str. 86. Tel.: +74991201114. E-mail: asenchukova@gmail.com
Akopova Nataliya Borisovna, Ph.D., Obstetrician-gynecologist of the Department of Radiation and instrumental diagnostics of tumor diseases of the reproductive organs, Russian Research Center of Roentgenology and Radiology, Ministry of Health of Russia. 117997 Russia, Moscow, Profsoyuznaya str. 86. Tel.: +74991206077
Aleksandrova Nataliya Vladimirovna, MD, Research Center of Obstetrics, Gynecology and Perinatology, Ministry of Health of Russia.
117997, Russia, Moscow, Ac. Oparina str. 4. E-mail: alexandrova.ncagip@gmail.com
Burmenskaya Olga Vladimirovna, MD, Senior Researcher of Laboratory molecular genetic factors, Research Center of Obstetrics, Gynecology and Perinatology,
Ministry of Health of Russia. 117997, Russia, Moscow, Ac. Oparina str. 4. Tel.: +79167531709. E-mail: bourmenska@mail.ru
Ashrafyan Levon Andreevich, MD, Professor, Head of the Department of Early carcinogenesis, prevention, diagnostics and comprehensive treatment of oncological diseases of female reproductive organs, Russian Research Center of Roentgenology and Radiology, Ministry of Health of Russia.
117997 Russia, Moscow, Profsoyuznaya str. 86. Tel.: +74953349909
For citations: Melnikova N.V., Bozhenko V.K., Antonova I.B., Babaeva N.A., Yarovaya N.Yu., Bolotina N.A., Zakharenko M.V., Senchukova A.L., Akopova N.B., Aleksandrova N.V., Burmenskaya O.V., Ashrafyan L.A. Cervical intraepithelial neoplasia: Analysis of mRNA profile in the practice of liquid-based cytology. Akusherstvo i Ginekologiya/Obstetrics and Gynecology. 2017; (4): 95-100. (in Russian)
http://dx.doi.org/10.18565/aig.2017.4.95-100
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