<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.3 20210610//EN" "JATS-journalpublishing1-3.dtd">
<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">transmed</journal-id><journal-title-group><journal-title xml:lang="ru">Трансляционная медицина</journal-title><trans-title-group xml:lang="en"><trans-title>Translational Medicine</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">2311-4495</issn><issn pub-type="epub">2410-5155</issn><publisher><publisher-name>Almazov National Medical Research Centre, Saint Petersburg, Russia</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.18705/2311-4495-2018-5-1-44-52</article-id><article-id custom-type="elpub" pub-id-type="custom">transmed-369</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>ОНКОЛОГИЯ</subject></subj-group></article-categories><title-group><article-title>ПРОЛИФЕРАТИВНАЯ АКТИВНОСТЬ (KI-67) И УРОВЕНЬ ЭКСПРЕССИИ ГЕНА СОСУДИСТО-ЭНДОТЕЛИАЛЬНОГО ФАКТОРА РОСТА (VEGF) В ГЕМИСТОЦИТАРНЫХ АСТРОЦИТОМАХ</article-title><trans-title-group xml:lang="en"><trans-title>THE PROLIFERATIVE ACTIVITY (KI-67) AND THE LEVEL OF VASCULAR ENDOTHELIAL GROWTH FACTOR (VEGF) GENE EXPRESSION IN GEMISTOCYTIC ASTROCYTOMAS</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0307-7842</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Зрелов</surname><given-names>А. А.</given-names></name><name name-style="western" xml:lang="en"><surname>Zrelov</surname><given-names>A. A.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Зрелов Андрей Андреевич - врач-нейрохирург «РНХИ им. проф. А.Л. Поленова», филиала ФГБУ НМИЦ им. В.А. Алмазова</p></bio><bio xml:lang="en"><p>Andrei А. Zrelov - neurosurgeon Polenov RSRIN, the branch of NMRC.</p><p> </p><p>Mayakovskaya str. 12, Saint Petersburg,  191014</p></bio><email xlink:type="simple">andrey.zrelov@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мацко</surname><given-names>М. В.</given-names></name><name name-style="western" xml:lang="en"><surname>Matsko</surname><given-names>M. V.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мацко Марина Витальевна - кандидат медицинских наук, с.н.с. отделения хирургии опухолей головного и спинного мозга №1 НИО нейрохирургии «РНХИ им. проф. А.Л. Поленова», филиала ФГБУ НМИЦ им. В.А. Алмазова</p></bio><bio xml:lang="en"><p>Marina V. Matsko - PhD, Senior Researcher, department of Neurooncology Polenov RSRIN, the branch of Almazov NMRC </p></bio><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Мацко</surname><given-names>Д. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Matsko</surname><given-names>D. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Мацко Дмитрий Евгеньевич - доктор медицинских наук, профессор, заместитель директора «СПб КНпЦСВМП(о)»</p></bio><bio xml:lang="en"/><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Улитин</surname><given-names>А. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Ulitin</surname><given-names>A. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Улитин Алексей Юрьевич - доктор медицинских наук, директор «РНХИ им. проф. А.Л. Поленова», филиала ФГБУ НМИЦ им. В.А. Алмазова</p></bio><bio xml:lang="en"><p>Aleksei Yu. Ulitin - PhD, Director of Polenov RSRIN, the branch of Almazov NMRC</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Бакшеева</surname><given-names>А. О.</given-names></name><name name-style="western" xml:lang="en"><surname>Baksheeva</surname><given-names>A. O.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Бакшеева Анастасия Олеговна - аспирант кафедры нейрохирургии им. проф. А.Л. Поленова ФГБОУ ВО СЗГМУ им. И.И. Мечникова</p></bio><bio xml:lang="en"><p>Anastasiya O. Baksheeva - postgraduate of NorthWestern State Medical University n. a. I.I. Mechnikov</p></bio><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Скляр</surname><given-names>С. С.</given-names></name><name name-style="western" xml:lang="en"><surname>Skliar</surname><given-names>S. S.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Скляр Софья Сергеевна - аспирант кафедры нейрохирургии.</p><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>Sof'ya S. Sklyar – postgraduate.</p><p>Saint Petersburg</p></bio><xref ref-type="aff" rid="aff-3"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Имянитов</surname><given-names>Е. Н.</given-names></name><name name-style="western" xml:lang="en"><surname>Imyanitov</surname><given-names>E. N.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Имянитов Евгений Наумович - член-корр. РАН, доктор медицинских наук, проф., заведующий научным отделом ФГБУ НМИЦ им. Н.Н. Петрова</p></bio><bio xml:lang="en"><p>Evgenii N. Imyanitov - PhD, prof., Head of science department N.N. Petrov RSRIN of Oncology</p></bio><xref ref-type="aff" rid="aff-4"/></contrib><contrib contrib-type="author" corresp="yes"><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Тастанбеков</surname><given-names>М. М.</given-names></name><name name-style="western" xml:lang="en"><surname>Tastanbekov</surname><given-names>M. M.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Тастанбеков Малик Маратович - доктор медицинских наук, руководитель отделения хирургии опухолей головного и спинного мозга №1 НИО нейрохирургии РНХИ им. проф. А.Л. Поленова, филиала ФГБУ НМИЦ им. В.А. Алмазова.</p><p>Санкт-Петербург</p></bio><bio xml:lang="en"><p>Malik M. Tastanbekov - PhD, Head of department of Neurooncology Polenov RSRIN, the branch of Almazov NMRC.</p><p>Saint Petersburg</p></bio><xref ref-type="aff" rid="aff-5"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>Российский научно-исследовательский нейрохирургический институт имени профессора А. Л. Поленова; Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России; Федеральное государственное бюджетное образовательное учреждение высшего образования «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Polenov Russian Scienific Research Institute of Neurosurgery; North-Western State Medical University named after I. I. Mechnikov</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>Российский научно-исследовательский нейрохирургический институт имени профессора А. Л. Поленова; Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России; Государственное бюджетное учреждение здравоохранения Санкт-Петербургский клинический научно-практический центр специализированных видов медицинской помощи (онкологический); Санкт-Петербургский Государственный Университет; Частное образовательное учреждение высшего образования Санкт-Петербургский медико-социальный институт</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Polenov Russian Scienific Research Institute of Neurosurgery; Saint-Petersburg Clinical Research Center Specialized Types of Medical Care; Saint Petersburg University; Saint-PetersburgMedico-Social Institute</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-3"><aff xml:lang="ru"><institution>Российский научно-исследовательский нейрохирургический институт имени профессора А. Л. Поленова; Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Polenov Russian Scienific Research Institute of Neurosurgery</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-4"><aff xml:lang="ru"><institution>Федеральное государственное бюджетное образовательное учреждение высшего образования «Северо-Западный государственный медицинский университет им. И.И. Мечникова» Минздрава России; Государственное бюджетное учреждение здравоохранения Санкт-Петербургский клинический научно-практический центр специализированных видов медицинской помощи (онкологический); Санкт-Петербургский Государственный Университет; Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр онкологии им. Н.Н. Петрова» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>North-Western State Medical University named after I. I. Mechnikov; Saint-Petersburg Clinical Research Center Specialized Types of Medical Care; Saint Petersburg University; N.N. Petrov National Medical Research Centre of Oncology</institution><country>Russian Federation</country></aff></aff-alternatives><aff-alternatives id="aff-5"><aff xml:lang="ru"><institution>Российский научно-исследовательский нейрохирургический институт имени профессора А. Л. Поленова; Федеральное государственное бюджетное учреждение «Национальный медицинский исследовательский центр им. В.А. Алмазова» Минздрава России</institution><country>Россия</country></aff><aff xml:lang="en"><institution>Polenov Russian Scienific Research Institute of Neurosurgery,</institution><country>Russian Federation</country></aff></aff-alternatives><pub-date pub-type="collection"><year>2018</year></pub-date><pub-date pub-type="epub"><day>26</day><month>04</month><year>2018</year></pub-date><volume>5</volume><issue>1</issue><fpage>44</fpage><lpage>52</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Зрелов А.А., Мацко М.В., Мацко Д.Е., Улитин А.Ю., Бакшеева А.О., Скляр С.С., Имянитов Е.Н., Тастанбеков М.М., 2018</copyright-statement><copyright-year>2018</copyright-year><copyright-holder xml:lang="ru">Зрелов А.А., Мацко М.В., Мацко Д.Е., Улитин А.Ю., Бакшеева А.О., Скляр С.С., Имянитов Е.Н., Тастанбеков М.М.</copyright-holder><copyright-holder xml:lang="en">Zrelov A.A., Matsko M.V., Matsko D.E., Ulitin A.Y., Baksheeva A.O., Skliar S.S., Imyanitov E.N., Tastanbekov M.M.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://transmed.almazovcentre.ru/jour/article/view/369">https://transmed.almazovcentre.ru/jour/article/view/369</self-uri><abstract><sec><title>Актуальность</title><p>Актуальность. Гемистоцитарные астроцитомы (ГА) – это вариант диффузных астроцитом GII (ВОЗ, 2016), который отличается более короткой общей выживаемостью пациентов по сравнению с диффузными астроцитомами. Роль экспрессии гена сосудисто-эндотелиального фактора роста (VEGF) и его связь с индексом пролиферативной активности (Ki-67) в ГА ранее не изучалась.</p></sec><sec><title>Цель</title><p>Цель. Оценить зависимость уровня экспрессии гена VEGF от Ki-67 в ГА.</p></sec><sec><title>Материал и методы</title><p>Материал и методы. Выполнен ретроспективный и проспективный анализ морфо-молекулярных характеристик опухолевой ткани 9 пациентов с диагнозом ГА. В работу вошли пациенты старше 18 лет с супратенториальной локализацией опухоли. Возраст пациентов был от 27 до 37 лет, медиана составила 32 года. Мужчин было 4. После оперативного вмешательства проводилось гистологическое, иммуногистохимическое (Ki-67 и GFAP) и молекулярно-генетическое исследования фрагментов опухоли (методом ПЦР в режиме реального времени). Определялся уровень экспрессии гена VEGF и наличие мутации в генах IDH1/IDH2. Гистологический диагноз ставился в соответствии с классификацией опухолей ЦНС ВОЗ (2016) и атласом AFIP (2007).</p></sec><sec><title>Результаты</title><p>Результаты. Чаще всего опухоль локализовалась в нескольких долях головного мозга (44,4%). Дебют заболевания в большинстве случаев начинался с эпилептического синдрома (55,6%). Индексу пролиферативной активности (Ki-67) более 5% (71,4% случаев) соответствовала умеренная пролиферация эндотелия сосудов при гистологическом исследовании (85,7%), средний/высокий уровень экспрессии гена VEGF (ПЦР) (кроме одного случая). У больных с низким Ki-67 (≤5%) уровень экспрессии гена VEGF был низким в 100% случаев, а пролиферация эндотелия сосудов отсутствовала.</p></sec><sec><title>Заключение</title><p>Заключение. Высокий Ki-67 (&gt;5%), пролиферация эндотелия сосудов, средний/высокий уровень экспрессии гена VEGF, которые наблюдались в 7 из 9 гемистоцитарных астроцитомах, являются характерными чертами астроцитом GIII. Таким образом, ГА – это неоднородная группа опухолей, и часть из них представлена злокачественной подгруппой.</p></sec></abstract><trans-abstract xml:lang="en"><sec><title>Background</title><p>Background. Gemistocytic astrocytomas (GA) are a variant of diffuse astrocytomas GII (WHO, 2016), which is characterized by a shorter overall survival of patients than diffuse astrocytoma. The role of vascular endothelial growth factor (VEGF) gene expression and its association with the index of proliferative activity (Ki-67) in GA has not been studied</p></sec><sec><title>Objective</title><p>Objective. To estimate the correlation of VEGF gene expression on Ki-67 in GA.</p></sec><sec><title>Design and methods</title><p>Design and methods. A retrospective and prospective analysis of morphological and molecular-genetic features of tumors was performed on 9 patients with the diagnosis of GA. Patients over 18 years of age with supratentorial tumor localization were included in the study. The patients were aged from 27 to 37 years, the median age was 32 years. There were 4 men. Fragments of tumor tissue obtained during surgery were subjected to histological, immunohistochemical (Ki-67 and GFAP) and molecular genetic studies. By real-time PCR method was used to determine the level of the VEGF gene expression and the presence of a mutation in IDH1/IDH2 genes. Histological diagnosis was made in accordance with the classification of tumors of the CNS WHO (2016) and the AFIP atlas (2007).</p></sec><sec><title>Results</title><p>Results. The tumor most often affected several lobes of the brain (44,4%). The first clinical manifestations of the disease in the vast majority of cases were epileptic and hypertensive syndromes (55,6%). For the proliferative activity index Ki-67 &gt;5% (71,4% of cases) the moderate proliferation of vascular endothelium was noted in 85,7% of cases and the middle/high level of VEGF gene expression (except one case). In patients with low Ki-67 (≤5%), the low level of the VEGF gene expression was determined in 100% cases, the proliferation of the vascular endothelium was absent.</p></sec><sec><title>Conclusion</title><p>Conclusion. High Ki-67 (&gt;5%), the proliferation of the vascular endothelium, middle/high level of VEGF gene expression are typical attributes of anaplastic astrocytomas. That’s why some GA have features of astrocytomas GIII.</p></sec></trans-abstract><kwd-group xml:lang="ru"><kwd>гемистоцитарная астроцитома</kwd><kwd>cосудисто-эндотелиальный фактор роста</kwd><kwd>индекс пролиферативной активности (Ki-67)</kwd><kwd>ген VEGF</kwd></kwd-group><kwd-group xml:lang="en"><kwd>gemistocytic astrocytoma</kwd><kwd>vascular endothelial growth factor</kwd><kwd>proliferative activity (Ki-67)</kwd><kwd>VEGF gene</kwd></kwd-group><funding-group><funding-statement xml:lang="ru">РФФИ, гранты № 15-04-17044 и № 17-54-12007; «именной грант проф. Э.Э. Эйхвальда ФГБОУ ВО СЗГМУ им. И.И. Мечникова» от 2017 г.</funding-statement></funding-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131(6):803-820.</mixed-citation><mixed-citation xml:lang="en">Louis DN, Perry A, Reifenberger G, et al. The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary. Acta Neuropathol. 2016;131(6):803-820.</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Ohta T, Kim YH, Oh JE, et al. Alterations of the RRAS and ERCC1 genes at 19q13 in gemistocytic astrocytomas. J Neuropathol Exp Neurol. 2014;73(10):908-915.</mixed-citation><mixed-citation xml:lang="en">Ohta T, Kim YH, Oh JE, et al. Alterations of the RRAS and ERCC1 genes at 19q13 in gemistocytic astrocytomas. J Neuropathol Exp Neurol. 2014;73(10):908-915.</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Simkin PM, Yang N, Tsui A, et al. Magnetic resonance imaging features of gemistocytic astrocytoma. J Med Imaging Radiat Oncol. 2016;60(6):733-740.</mixed-citation><mixed-citation xml:lang="en">Simkin PM, Yang N, Tsui A, et al. Magnetic resonance imaging features of gemistocytic astrocytoma. J Med Imaging Radiat Oncol. 2016;60(6):733-740.</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Sahm F, Korshunov A, Schrimpf D, et al. Gain of 12p encompassing CCND2 is associated with gemistocytic histology in IDH mutant astrocytomas. Acta Neuropathol. 2017;133(2):325-327.</mixed-citation><mixed-citation xml:lang="en">Sahm F, Korshunov A, Schrimpf D, et al. Gain of 12p encompassing CCND2 is associated with gemistocytic histology in IDH mutant astrocytomas. Acta Neuropathol. 2017;133(2):325-327.</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Avninder S, Sharma MC, Deb P, et al. Gemistocytic astrocytomas: histomorphology, proliferative potential and genetic alterations--a study of 32 cases. J Neurooncol. 2006;78(2):123-127.</mixed-citation><mixed-citation xml:lang="en">Avninder S, Sharma MC, Deb P, et al. Gemistocytic astrocytomas: histomorphology, proliferative potential and genetic alterations--a study of 32 cases. J Neurooncol. 2006;78(2):123-127.</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Tihan T, Vohra P, Berger MS, Keles GE. Definition and diagnostic implications of gemistocytic astrocytomas: a pathological perspective. J Neurooncol. 2006;76(2):175-183.</mixed-citation><mixed-citation xml:lang="en">Tihan T, Vohra P, Berger MS, Keles GE. Definition and diagnostic implications of gemistocytic astrocytomas: a pathological perspective. J Neurooncol. 2006;76(2):175-183.</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Babu R, Bagley JH, Park JG, et al. Low-grade astrocytomas: the prognostic value of fibrillary, gemistocytic, and protoplasmic tumor histology. J Neurosurg. 2013;119(2):434-441.</mixed-citation><mixed-citation xml:lang="en">Babu R, Bagley JH, Park JG, et al. Low-grade astrocytomas: the prognostic value of fibrillary, gemistocytic, and protoplasmic tumor histology. J Neurosurg. 2013;119(2):434-441.</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Okamoto Y, Di Patre PL, Burkhard C, et al. Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas. Acta Neuropathol. 2004;108(1):49-56.</mixed-citation><mixed-citation xml:lang="en">Okamoto Y, Di Patre PL, Burkhard C, et al. Population-based study on incidence, survival rates, and genetic alterations of low-grade diffuse astrocytomas and oligodendrogliomas. Acta Neuropathol. 2004;108(1):49-56.</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Nowak-Sadzikowska J, Gliński B, Szpytma T, Pluta E. Postoperative irradiation of incompletely excised gemistocytic astrocytomas. Clinical outcome and prognostic factors. Strahlenther Onkol. 2005;181(4):246-250.</mixed-citation><mixed-citation xml:lang="en">Nowak-Sadzikowska J, Gliński B, Szpytma T, Pluta E. Postoperative irradiation of incompletely excised gemistocytic astrocytomas. Clinical outcome and prognostic factors. Strahlenther Onkol. 2005;181(4):246-250.</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Martins DC, Malheiros SM, Santiago LH, Stávale JN. Gemistocytes in astrocytomas: are they a significant prognostic factor? J Neurooncol. 2006;80(1):49-55.</mixed-citation><mixed-citation xml:lang="en">Martins DC, Malheiros SM, Santiago LH, Stávale JN. Gemistocytes in astrocytomas: are they a significant prognostic factor? J Neurooncol. 2006;80(1):49-55.</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Kösel S, Scheithauer BW, Graeber MB. Genotypephenotype correlation in gemistocytic astrocytomas. Neurosurgery. 2001;48(1):187-193;</mixed-citation><mixed-citation xml:lang="en">Kösel S, Scheithauer BW, Graeber MB. Genotypephenotype correlation in gemistocytic astrocytomas. Neurosurgery. 2001;48(1):187-193;</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Reis RM, Hara A, Kleihues P, Ohgaki H. Genetic evidence of the neoplastic nature of gemistocytes in astrocytomas. Acta Neuropathol. 2001;102(5):422-425.</mixed-citation><mixed-citation xml:lang="en">Reis RM, Hara A, Kleihues P, Ohgaki H. Genetic evidence of the neoplastic nature of gemistocytes in astrocytomas. Acta Neuropathol. 2001;102(5):422-425.</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Watanabe K, Peraud A, Gratas C, et al. p53 and PTEN gene mutations in gemistocytic astrocytomas. Acta Neuropathol. 1998;95(6):559-64.</mixed-citation><mixed-citation xml:lang="en">Watanabe K, Peraud A, Gratas C, et al. p53 and PTEN gene mutations in gemistocytic astrocytomas. Acta Neuropathol. 1998;95(6):559-64.</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Kros JM, Waarsenburg N, Hayes DP, et al. Cytogenetic analysis of gemistocytic cells in gliomas. J Neuropathol Exp Neurol. 2000; 59:679–686.</mixed-citation><mixed-citation xml:lang="en">Kros JM, Waarsenburg N, Hayes DP, et al. Cytogenetic analysis of gemistocytic cells in gliomas. J Neuropathol Exp Neurol. 2000; 59:679–686.</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">Kros JM, Schouten WC, Janssen PJ, van der Kwast TH. Proliferation of gemistocytic cells and glial fibrillary acidic protein (GFAP)-positive oligodendroglial cells in gliomas: a MIB-1/GFAP double labeling study. Acta Neuropathol. 1996;91(1):99-103.</mixed-citation><mixed-citation xml:lang="en">Kros JM, Schouten WC, Janssen PJ, van der Kwast TH. Proliferation of gemistocytic cells and glial fibrillary acidic protein (GFAP)-positive oligodendroglial cells in gliomas: a MIB-1/GFAP double labeling study. Acta Neuropathol. 1996;91(1):99-103.</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">Krouwer HGJ, Davis RL, Silver P, et al. Gemistocytic astrocytomas: a reappraisal. J Neurosurg. 1991;74:399–406.</mixed-citation><mixed-citation xml:lang="en">Krouwer HGJ, Davis RL, Silver P, et al. Gemistocytic astrocytomas: a reappraisal. J Neurosurg. 1991;74:399–406.</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">Elvidge AR, Martinez-Coll A. Long-Term FollowUp of 106 Cases of Astrocytoma, 1928–1939. J Neurosurg. 1956;13:230–243.</mixed-citation><mixed-citation xml:lang="en">Elvidge AR, Martinez-Coll A. Long-Term FollowUp of 106 Cases of Astrocytoma, 1928–1939. J Neurosurg. 1956;13:230–243.</mixed-citation></citation-alternatives></ref><ref id="cit18"><label>18</label><citation-alternatives><mixed-citation xml:lang="ru">Ohgaki H, Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 2005; 64:479–89.</mixed-citation><mixed-citation xml:lang="en">Ohgaki H, Kleihues P. Population-based studies on incidence, survival rates, and genetic alterations in astrocytic and oligodendroglial gliomas. J Neuropathol Exp Neurol. 2005; 64:479–89.</mixed-citation></citation-alternatives></ref><ref id="cit19"><label>19</label><citation-alternatives><mixed-citation xml:lang="ru">Heo YJ, Park JE, Kim HS, et al. Prognostic relevance of gemistocytic grade II astrocytoma: gemistocytic component and MR imaging features compared to non-gemistocytic grade II astrocytoma. Eur Radiol.2017;27(7):3022-3032.</mixed-citation><mixed-citation xml:lang="en">Heo YJ, Park JE, Kim HS, et al. Prognostic relevance of gemistocytic grade II astrocytoma: gemistocytic component and MR imaging features compared to non-gemistocytic grade II astrocytoma. Eur Radiol.2017;27(7):3022-3032.</mixed-citation></citation-alternatives></ref><ref id="cit20"><label>20</label><citation-alternatives><mixed-citation xml:lang="ru">Burger PC MD, Scheithauer BW. 7: Tumors of the Central Nervous System. 1 edition. Washington, DC: Amer Registry of Pathology, 2007.</mixed-citation><mixed-citation xml:lang="en">Burger PC MD, Scheithauer BW. 7: Tumors of the Central Nervous System. 1 edition. Washington, DC: Amer Registry of Pathology, 2007.</mixed-citation></citation-alternatives></ref><ref id="cit21"><label>21</label><citation-alternatives><mixed-citation xml:lang="ru">Mitiushkina NV, Iyevleva AG, Poltoratskiy AN, et al. Detection of EGFR mutations and EML4-ALK rearrangements in lung adenocarcinomas using archived cytological slides. Cancer Cytopathol. 2013;121(7):370-6.</mixed-citation><mixed-citation xml:lang="en">Mitiushkina NV, Iyevleva AG, Poltoratskiy AN, et al. Detection of EGFR mutations and EML4-ALK rearrangements in lung adenocarcinomas using archived cytological slides. Cancer Cytopathol. 2013;121(7):370-6.</mixed-citation></citation-alternatives></ref><ref id="cit22"><label>22</label><citation-alternatives><mixed-citation xml:lang="ru">Brandes AA, Nicolardi L, Tosoni A, et al. Survival following adjuvant PCV or temozolomide for anaplastic astrocytoma. Neuro Oncol. 2006;8(3):253-60.</mixed-citation><mixed-citation xml:lang="en">Brandes AA, Nicolardi L, Tosoni A, et al. Survival following adjuvant PCV or temozolomide for anaplastic astrocytoma. Neuro Oncol. 2006;8(3):253-60.</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
