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Роль иммуногистохимического исследования при диагностике опухолевых поражений шейки матки
Роль иммуногистохимического исследования при диагностике опухолевых поражений шейки матки
Щеголев А.И., Мишнев О.Д. Роль иммуногистохимического исследования при диагностике опухолевых поражений шейки матки. Гинекология. 2016; 18 (6): 24–27.
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Аннотация
Проведен анализ данных литературы о возможностях применения иммуногистохимических маркеров для диагностики и дифференциальной диагностики поражений шейки матки. Наиболее существенную помощь в выявлении и определении степени цервикальной интраэпителиальной неоплазии оказывает иммуногистохимическое выявление Ki-67 и р16. Показаны изменения р63, топоизомеразы, C-erbB-2, циклина D1 при цервикальной интраэпителиальной неоплазии разной степени выраженности и раке шейки матки. Сделан вывод, что иммуногистохимическое исследование закономерно считается эффективным методом патогистологического исследования, позволяющим проводить объективную диагностику опухолевых поражений шейки матки, дифференциальную их диагностику с реактивными и опухолеподобными изменениями, а также определять прогноз заболевания.
Ключевые слова: шейка матки, цервикальная интраэпителиальная неоплазия, рак, иммуногистохимия.
Key words: cervix, cervical intraepithelial neoplasia, cancer, immunohistochemistry.
Ключевые слова: шейка матки, цервикальная интраэпителиальная неоплазия, рак, иммуногистохимия.
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Key words: cervix, cervical intraepithelial neoplasia, cancer, immunohistochemistry.
Полный текст
Список литературы
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24. Kalof AN, Cooper K. Our approach to squamous intraepithelial lesions of the uterine cervix. J Clin Pathol 2007; 60: 449–55.
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27. Shi J, Liu H, Wilkerson M et al. Evaluation of p16, MCM2, DNA Topoisomerase IIA and ProExC in cervical squamous intraepithelial lesions. Lab Investig 2007; 87 (Suppl. 1): 214A.
28. Badr RE, Walts AE, Chung F et al. A sensitive and specific marker of HPV-associated squamous lesions of the cervix. Am J Surg Pathol 2008; 32: 899–906.
29. Niibe Y, Nakano T, Ohno T et al. Prognostic significance of c-erbB-2/Her2 expression in advanced uterine cervical carcinoma with para-aortic lymph node metastasis treated with radiation therapy. Int J Gynecol Cancer 2003; 13: 849–55.
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33. Pinto AP, Schlecht NF, Woo TY et al. Biomarker (ProEx C, p16(INK4A), and MiB-1) distinction of high-grade squamous intraepithelial lesion from its mimics. Mod Pathol 2008; 21: 1067–74.
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2. Sostoyanie onkologicheskoy pomoshchi naseleniyu Rossii v 2015 godu. Pod red. A.D.Kaprina, V.V.Starinskogo, G.V.Petrovoy. M.: MNIOI im. P.A.Gertsena – filial FGBU «NMIRTs» Minzdrava Rossii, 2016. [in Russian]
3. Prilepskaya V.N., Kogan E.A., Trofimov D.Yu. Vozmozhnosti diagnostiki i lecheniya zabolevaniy sheyki matki. Akusherstvo i ginekologiya. 2013; 9: 90–6. [in Russian]
4. Bayramova G.R., Fayzullin L.Z., Korol'kova A.I. i dr. Skrining raka sheyki matki: chto novogo v mirovoy praktike. Akusherstvo i ginekologiya. 2016; 7: 17–21. [in Russian]
5. Opukholi sheyki matki. Morfologicheskaya diagnostika i genetika. Pod red. Yu.Yu.Andreevoy, G.A.Franka. M.: Prakticheskaya meditsina, 2012. [in Russian]
6. Rukovodstvo po immunogistokhimicheskoy diagnostike opukholey cheloveka. Pod red. S.V.Petrova, N.T.Raykhlina. Kazan', 2012. [in Russian]
7. WHO classification of tumours of female reproductive organs. Ed. R.J.Kurman, M.L.Carcangiu, C.S.Herrington, R.H.Young. IARC: Lyon, 2014.
8. Moscicki AB, Ma Y, Wibbelsman C et al. Rate of and risks for regression of cervical intraepithelial neoplasia 2 in adolescentsand young women. Obstet Gynecol 2010; 116: 1373–80.
9. Goldie SJ, Kohli M, Grima D et al. Projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 vaccine. J Natl Cancer Inst 2004; 96: 604–15.
10. Resnick M, Lester S, Tate JE et al. Viral and histopathological correlates on MN and MIB-1 expression in cervical intra-epithelial neoplasia. Hum Pathol 1996; 27: 234–9.
11. Maeda MY, Simoes M, Wakamatsu A. Relevance of the rates of PCNA, Ki-67 and p53 expression according to the epithelial compartment in cervical lesions. Pathologica 2001; 93: 189–95.
12. Alameda F, Fuste P, Boluda S et al. The Ki67 labeling Index is not a useful predictor for the follow up of cervical Intraepithelial Neoplasia-1. J Low Gen Tract Dis 2004; 8: 313–6.
13. Carreras R, Alameda F, Mancebo G et al. A study of Ki-67, c-erbB2 and cyclin D-1 expression in CIN-I, CIN-III and squamous cell carcinoma of the cervix. Histol Histopathol 2007; 22: 587–92.
14. Kruse AJ, Baak JP, Janssen EA et al. Low- and high-risk CIN 1 and 2 lesions: prospective predictive value of grade, HPV, and Ki-67 immuno-quantitative variables. J Pathol 2003; 199: 462–70.
15. Kruse AJ, Baak JP, Janssen EA et al. Ki67 predicts progression in early CIN: validation of a multivariate progression-risk model. Cell Oncol 2004; 26: 13–20.
16. Keating JT, Ince T, Crum CP. Surrogate biomarkers of HPV infection in cervical neoplasia screening and diagnosis. Adv Anat Pathol 2001; 8: 83–92.
17. Bose S, Evans H, Lantzy L et al. p16(INK4A) is a surrogate biomarker for a subset of human papilloma virus-associated dysplasias of the uterine cervix as determined on the Pap smear. Diagn Cytopathol 2005; 32: 21–4.
18. Murphy N, Ring M, Heffron CC et al. p16INK4A, CDC6, and MCM5: predictive biomarkers in cervical preinvasive neoplasiaand cervical cancer. J Clin Pathol 2005; 58: 525–34.
19. Tsoumpou I, Arbyn M, Kyrgiou M et al. p16(INK4a) immunostaining in cytological and histological specimens from theuterine cervix: a systematic review and metaanalysis. Cancer Treat Rev 2009; 35: 210–20.
20. Dray M, Russell P, Dalrymple C et al. p16(INK4a) as a complementary marker of high-grade intraepithelial lesions of the uterine cervix. I: experience with squamous lesions in 189 consecutive cervical biopsies. Pathology 2005; 37: 112–24.
21. Dijkstra MG, Heideman DA, de Roy SC et al. p16(INK4a) immunostaining as an alternative to histology review for reliable grading of cervical intraepithelial lesions. J Clin Pathol 2010; 63: 972–7.
22. Negri G, Vittadello F, Romano F et al. p16INK4a expression and progression risk of low-grade intraepithelial neoplasia of the cervix uteri. Virchows Arch 2004; 445: 616–20.
23. Klaes R, Friedrich T, Spitkovsky D et al. Overexpression of p16(INK4A) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer 2001; 92: 276–84.
24. Kalof AN, Cooper K. Our approach to squamous intraepithelial lesions of the uterine cervix. J Clin Pathol 2007; 60: 449–55.
25. Vorotelyak E.A., Chermnykh E.S., Tkachenko S.B. i dr. Ekspressiya i funktsiya gena r63 v epitelial'nykh kletkakh. Izvestiya RAN. 2007; 4: 389–93. [in Russian]
26. Selvi K, Badhe BA, Papa D et al. Role of p16, CK17, p63, and Human Papilloma virus in diagnosis of cervical intraepithelial neoplasia and distinction from its mimics. Internat J Surg Pathol 2014; 22: 221–30.
27. Shi J, Liu H, Wilkerson M et al. Evaluation of p16, MCM2, DNA Topoisomerase IIA and ProExC in cervical squamous intraepithelial lesions. Lab Investig 2007; 87 (Suppl. 1): 214A.
28. Badr RE, Walts AE, Chung F et al. A sensitive and specific marker of HPV-associated squamous lesions of the cervix. Am J Surg Pathol 2008; 32: 899–906.
29. Niibe Y, Nakano T, Ohno T et al. Prognostic significance of c-erbB-2/Her2 expression in advanced uterine cervical carcinoma with para-aortic lymph node metastasis treated with radiation therapy. Int J Gynecol Cancer 2003; 13: 849–55.
30. Bae DS, Cho SB, Kim YJ et al. Aberrant expression of cyclin D1 is associated with poor prognosis in early stage cervical cancer of the uterus. Gynecol Oncol 2001; 81: 341–7.
31. Rose PG, Cibas ES, Rose PG, Peters WA. III. Cervical squamous neoplasia. In: C.P.Crum, M.R.Nucci, K.R.Lee, eds. Diagnostic Gynecologic and Obstetric Pathology. 2nd ed. Philadelphia, PA: Elsevier Saunders, 2011; p. 245–327.
32. Herfs M, Yamamoto Y, Laury A et al. A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer. Proc Natl Acad Sci USA 2012; 109: 10516–21.
33. Pinto AP, Schlecht NF, Woo TY et al. Biomarker (ProEx C, p16(INK4A), and MiB-1) distinction of high-grade squamous intraepithelial lesion from its mimics. Mod Pathol 2008; 21: 1067–74.
34. Singer G, Kurman RJ, McMaster MT et al. HLA-G immunoreactivity is specific for intermediate trophoblast in gestational trophoblastic disease and can serve as a useful marker in differential diagnosis. Am J Surg Pathol 2002; 26: 914–20.
35. Ou-Yang RJ, Hui P, Yang XJ, Zynger DL. Expression of glypican 3 in placental site trophoblastic tumor. Diagn Pathol 2010; 5: 64.
36. Kindelberger DW, Krane JE, Lee KR. Glandular neoplasia of the cervix In: C.P.Crum, M.R.Nucci, K.R.Lee, eds. Diagnostic Gynecologic and Obstetric Pathology. 2nd ed. Philadelphia, PA: Elsevier Saunders, 2011; p. 328–78.
37. Witkiewicz A, Lee KR, Brodsky G et al. Superficial (early) endocervical adenocarcinoma in situ: a study of 12 cases and comparison to conventional AIS. Am J Surg Pathol 2005; 29: 1609–14.
38. Ishikawa M, Fujii T, Masumoto N et al. Correlation of p16INK4A overexpression with human papillomavirus infection in cervical adenocarcinomas. Int J Gynecol Pathol 2003; 22: 378–85.
39. Kong CS, Beck AH, Longacre TA. A panel of 3 markers including p16, ProExC, or HPV ISH is optimal for distinguishing between primary endometrial and endocervical adenocarcinomas. Am J Surg Pathol 2010; 34: 915–26.
40. McCluggage WG. Ten problematic issues identified by pathology review for multidisciplinary gynaecological oncology meetings. J Clin Pathol 2012; 65: 293–301.
2. Состояние онкологической помощи населению России в 2015 году. Под ред. А.Д.Каприна, В.В.Старинского, Г.В.Петровой. М.: МНИОИ им. П.А.Герцена – филиал ФГБУ «НМИРЦ» Минздрава России, 2016. / Sostoyanie onkologicheskoy pomoshchi naseleniyu Rossii v 2015 godu. Pod red. A.D.Kaprina, V.V.Starinskogo, G.V.Petrovoy. M.: MNIOI im. P.A.Gertsena – filial FGBU «NMIRTs» Minzdrava Rossii, 2016. [in Russian]
3. Прилепская В.Н., Коган Е.А., Трофимов Д.Ю. Возможности диагностики и лечения заболеваний шейки матки. Акушерство и гинекология. 2013; 9: 90–6. / Prilepskaya V.N., Kogan E.A., Trofimov D.Yu. Vozmozhnosti diagnostiki i lecheniya zabolevaniy sheyki matki. Akusherstvo i ginekologiya. 2013; 9: 90–6. [in Russian]
4. Байрамова Г.Р., Файзуллин Л.З., Королькова А.И. и др. Скрининг рака шейки матки: что нового в мировой практике. Акушерство и гинекология. 2016; 7: 17–21. / Bayramova G.R., Fayzullin L.Z., Korol'kova A.I. i dr. Skrining raka sheyki matki: chto novogo v mirovoy praktike. Akusherstvo i ginekologiya. 2016; 7: 17–21. [in Russian]
5. Опухоли шейки матки. Морфологическая диагностика и генетика. Под ред. Ю.Ю.Андреевой, Г.А.Франка. М.: Практическая медицина, 2012. / Opukholi sheyki matki. Morfologicheskaya diagnostika i genetika. Pod red. Yu.Yu.Andreevoy, G.A.Franka. M.: Prakticheskaya meditsina, 2012. [in Russian]
6. Руководство по иммуногистохимической диагностике опухолей человека. Под ред. С.В.Петрова, Н.Т.Райхлина. Казань, 2012. / Rukovodstvo po immunogistokhimicheskoy diagnostike opukholey cheloveka. Pod red. S.V.Petrova, N.T.Raykhlina. Kazan', 2012. [in Russian]
7. WHO classification of tumours of female reproductive organs. Ed. R.J.Kurman, M.L.Carcangiu, C.S.Herrington, R.H.Young. IARC: Lyon, 2014.
8. Moscicki AB, Ma Y, Wibbelsman C et al. Rate of and risks for regression of cervical intraepithelial neoplasia 2 in adolescentsand young women. Obstet Gynecol 2010; 116: 1373–80.
9. Goldie SJ, Kohli M, Grima D et al. Projected clinical benefits and cost-effectiveness of a human papillomavirus 16/18 vaccine. J Natl Cancer Inst 2004; 96: 604–15.
10. Resnick M, Lester S, Tate JE et al. Viral and histopathological correlates on MN and MIB-1 expression in cervical intra-epithelial neoplasia. Hum Pathol 1996; 27: 234–9.
11. Maeda MY, Simoes M, Wakamatsu A. Relevance of the rates of PCNA, Ki-67 and p53 expression according to the epithelial compartment in cervical lesions. Pathologica 2001; 93: 189–95.
12. Alameda F, Fuste P, Boluda S et al. The Ki67 labeling Index is not a useful predictor for the follow up of cervical Intraepithelial Neoplasia-1. J Low Gen Tract Dis 2004; 8: 313–6.
13. Carreras R, Alameda F, Mancebo G et al. A study of Ki-67, c-erbB2 and cyclin D-1 expression in CIN-I, CIN-III and squamous cell carcinoma of the cervix. Histol Histopathol 2007; 22: 587–92.
14. Kruse AJ, Baak JP, Janssen EA et al. Low- and high-risk CIN 1 and 2 lesions: prospective predictive value of grade, HPV, and Ki-67 immuno-quantitative variables. J Pathol 2003; 199: 462–70.
15. Kruse AJ, Baak JP, Janssen EA et al. Ki67 predicts progression in early CIN: validation of a multivariate progression-risk model. Cell Oncol 2004; 26: 13–20.
16. Keating JT, Ince T, Crum CP. Surrogate biomarkers of HPV infection in cervical neoplasia screening and diagnosis. Adv Anat Pathol 2001; 8: 83–92.
17. Bose S, Evans H, Lantzy L et al. p16(INK4A) is a surrogate biomarker for a subset of human papilloma virus-associated dysplasias of the uterine cervix as determined on the Pap smear. Diagn Cytopathol 2005; 32: 21–4.
18. Murphy N, Ring M, Heffron CC et al. p16INK4A, CDC6, and MCM5: predictive biomarkers in cervical preinvasive neoplasiaand cervical cancer. J Clin Pathol 2005; 58: 525–34.
19. Tsoumpou I, Arbyn M, Kyrgiou M et al. p16(INK4a) immunostaining in cytological and histological specimens from theuterine cervix: a systematic review and metaanalysis. Cancer Treat Rev 2009; 35: 210–20.
20. Dray M, Russell P, Dalrymple C et al. p16(INK4a) as a complementary marker of high-grade intraepithelial lesions of the uterine cervix. I: experience with squamous lesions in 189 consecutive cervical biopsies. Pathology 2005; 37: 112–24.
21. Dijkstra MG, Heideman DA, de Roy SC et al. p16(INK4a) immunostaining as an alternative to histology review for reliable grading of cervical intraepithelial lesions. J Clin Pathol 2010; 63: 972–7.
22. Negri G, Vittadello F, Romano F et al. p16INK4a expression and progression risk of low-grade intraepithelial neoplasia of the cervix uteri. Virchows Arch 2004; 445: 616–20.
23. Klaes R, Friedrich T, Spitkovsky D et al. Overexpression of p16(INK4A) as a specific marker for dysplastic and neoplastic epithelial cells of the cervix uteri. Int J Cancer 2001; 92: 276–84.
24. Kalof AN, Cooper K. Our approach to squamous intraepithelial lesions of the uterine cervix. J Clin Pathol 2007; 60: 449–55.
25. Воротеляк Е.А., Чермных Э.С., Ткаченко С.Б. и др. Экспрессия и функция гена р63 в эпителиальных клетках. Известия РАН. 2007; 4: 389–93. / Vorotelyak E.A., Chermnykh E.S., Tkachenko S.B. i dr. Ekspressiya i funktsiya gena r63 v epitelial'nykh kletkakh. Izvestiya RAN. 2007; 4: 389–93. [in Russian]
26. Selvi K, Badhe BA, Papa D et al. Role of p16, CK17, p63, and Human Papilloma virus in diagnosis of cervical intraepithelial neoplasia and distinction from its mimics. Internat J Surg Pathol 2014; 22: 221–30.
27. Shi J, Liu H, Wilkerson M et al. Evaluation of p16, MCM2, DNA Topoisomerase IIA and ProExC in cervical squamous intraepithelial lesions. Lab Investig 2007; 87 (Suppl. 1): 214A.
28. Badr RE, Walts AE, Chung F et al. A sensitive and specific marker of HPV-associated squamous lesions of the cervix. Am J Surg Pathol 2008; 32: 899–906.
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33. Pinto AP, Schlecht NF, Woo TY et al. Biomarker (ProEx C, p16(INK4A), and MiB-1) distinction of high-grade squamous intraepithelial lesion from its mimics. Mod Pathol 2008; 21: 1067–74.
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35. Ou-Yang RJ, Hui P, Yang XJ, Zynger DL. Expression of glypican 3 in placental site trophoblastic tumor. Diagn Pathol 2010; 5: 64.
36. Kindelberger DW, Krane JE, Lee KR. Glandular neoplasia of the cervix In: C.P.Crum, M.R.Nucci, K.R.Lee, eds. Diagnostic Gynecologic and Obstetric Pathology. 2nd ed. Philadelphia, PA: Elsevier Saunders, 2011; p. 328–78.
37. Witkiewicz A, Lee KR, Brodsky G et al. Superficial (early) endocervical adenocarcinoma in situ: a study of 12 cases and comparison to conventional AIS. Am J Surg Pathol 2005; 29: 1609–14.
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39. Kong CS, Beck AH, Longacre TA. A panel of 3 markers including p16, ProExC, or HPV ISH is optimal for distinguishing between primary endometrial and endocervical adenocarcinomas. Am J Surg Pathol 2010; 34: 915–26.
40. McCluggage WG. Ten problematic issues identified by pathology review for multidisciplinary gynaecological oncology meetings. J Clin Pathol 2012; 65: 293–301.
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27. Shi J, Liu H, Wilkerson M et al. Evaluation of p16, MCM2, DNA Topoisomerase IIA and ProExC in cervical squamous intraepithelial lesions. Lab Investig 2007; 87 (Suppl. 1): 214A.
28. Badr RE, Walts AE, Chung F et al. A sensitive and specific marker of HPV-associated squamous lesions of the cervix. Am J Surg Pathol 2008; 32: 899–906.
29. Niibe Y, Nakano T, Ohno T et al. Prognostic significance of c-erbB-2/Her2 expression in advanced uterine cervical carcinoma with para-aortic lymph node metastasis treated with radiation therapy. Int J Gynecol Cancer 2003; 13: 849–55.
30. Bae DS, Cho SB, Kim YJ et al. Aberrant expression of cyclin D1 is associated with poor prognosis in early stage cervical cancer of the uterus. Gynecol Oncol 2001; 81: 341–7.
31. Rose PG, Cibas ES, Rose PG, Peters WA. III. Cervical squamous neoplasia. In: C.P.Crum, M.R.Nucci, K.R.Lee, eds. Diagnostic Gynecologic and Obstetric Pathology. 2nd ed. Philadelphia, PA: Elsevier Saunders, 2011; p. 245–327.
32. Herfs M, Yamamoto Y, Laury A et al. A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer. Proc Natl Acad Sci USA 2012; 109: 10516–21.
33. Pinto AP, Schlecht NF, Woo TY et al. Biomarker (ProEx C, p16(INK4A), and MiB-1) distinction of high-grade squamous intraepithelial lesion from its mimics. Mod Pathol 2008; 21: 1067–74.
34. Singer G, Kurman RJ, McMaster MT et al. HLA-G immunoreactivity is specific for intermediate trophoblast in gestational trophoblastic disease and can serve as a useful marker in differential diagnosis. Am J Surg Pathol 2002; 26: 914–20.
35. Ou-Yang RJ, Hui P, Yang XJ, Zynger DL. Expression of glypican 3 in placental site trophoblastic tumor. Diagn Pathol 2010; 5: 64.
36. Kindelberger DW, Krane JE, Lee KR. Glandular neoplasia of the cervix In: C.P.Crum, M.R.Nucci, K.R.Lee, eds. Diagnostic Gynecologic and Obstetric Pathology. 2nd ed. Philadelphia, PA: Elsevier Saunders, 2011; p. 328–78.
37. Witkiewicz A, Lee KR, Brodsky G et al. Superficial (early) endocervical adenocarcinoma in situ: a study of 12 cases and comparison to conventional AIS. Am J Surg Pathol 2005; 29: 1609–14.
38. Ishikawa M, Fujii T, Masumoto N et al. Correlation of p16INK4A overexpression with human papillomavirus infection in cervical adenocarcinomas. Int J Gynecol Pathol 2003; 22: 378–85.
39. Kong CS, Beck AH, Longacre TA. A panel of 3 markers including p16, ProExC, or HPV ISH is optimal for distinguishing between primary endometrial and endocervical adenocarcinomas. Am J Surg Pathol 2010; 34: 915–26.
40. McCluggage WG. Ten problematic issues identified by pathology review for multidisciplinary gynaecological oncology meetings. J Clin Pathol 2012; 65: 293–301.
Авторы
А.И.Щеголев*1,2, О.Д.Мишнев2
1. ФГБУ Научный центр акушерства, гинекологии и перинатологии им. акад. В.И.Кулакова Минздрава России. 117997, Россия, Москва, ул. Академика Опарина, д. 4;
2. ФГБОУ ВО Российский национальный исследовательский медицинский университет им. Н.И.Пирогова Минздрава России. 117997, Россия, Москва, ул. Островитянова, д. 1
*ashegolev@oparina4.ru
1. Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Akademika Oparina, d. 4;
2. N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation,
Moscow, ul. Ostrovitianova, d. 1
*ashegolev@oparina4.ru
1. ФГБУ Научный центр акушерства, гинекологии и перинатологии им. акад. В.И.Кулакова Минздрава России. 117997, Россия, Москва, ул. Академика Опарина, д. 4;
2. ФГБОУ ВО Российский национальный исследовательский медицинский университет им. Н.И.Пирогова Минздрава России. 117997, Россия, Москва, ул. Островитянова, д. 1
*ashegolev@oparina4.ru
________________________________________________
1. Research Center for Obstetrics, Gynecology and Perinatology of the Ministry of Health of the Russian Federation. 117997, Russian Federation, Moscow, ul. Akademika Oparina, d. 4;
2. N.I.Pirogov Russian National Research Medical University of the Ministry of Health of the Russian Federation. 117997, Russian Federation,
Moscow, ul. Ostrovitianova, d. 1
*ashegolev@oparina4.ru
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