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<article 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" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Almanac of Clinical Medicine</journal-id><journal-title-group><journal-title xml:lang="en">Almanac of Clinical Medicine</journal-title><trans-title-group xml:lang="ru"><trans-title>Альманах клинической медицины</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2072-0505</issn><issn publication-format="electronic">2587-9294</issn><publisher><publisher-name xml:lang="en">Moscow Regional Research and Clinical Institute (MONIKI)</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">451</article-id><article-id pub-id-type="doi">10.18786/2072-0505-2016-44-5-613-623</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>ARTICLES</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">THE PROGNOSTIC AND DIFFERENTIAL DIAGNOSTIC VALUE OF CYTOKERATIN 7 AND 19, AND THYROID TRANSCRIPTION FACTOR-1 EXPRESSION IN LUNG NEUROENDOCRINE TUMORS OF VARIOUS GRADES</article-title><trans-title-group xml:lang="ru"><trans-title>ПРОГНОСТИЧЕСКОЕ И ДИФФЕРЕНЦИАЛЬНО-ДИАГНОСТИЧЕСКОЕ ЗНАЧЕНИЕ ЭКСПРЕССИИ ЦИТОКЕРАТИНОВ 7 И 19 И ТИРЕОИДНОГО ФАКТОРА ТРАНСКРИПЦИИ-1 В НЕЙРОЭНДОКРИННЫХ ОПУХОЛЯХ ЛЕГКИХ РАЗНОЙ СТЕПЕНИ ЗЛОКАЧЕСТВЕННОСТИ</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Gurevich</surname><given-names>L. E.</given-names></name><name xml:lang="ru"><surname>Гуревич</surname><given-names>Л. Е.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>ScD in Biology, Professor, Leading Research Fellow, Department of Pathological Anatomy</p></bio><bio xml:lang="ru"><p>д-р биол. наук, профессор, вед. науч. сотр. патологоанатомического отделения</p></bio><email>larisgur@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Korsakova</surname><given-names>N. A.</given-names></name><name xml:lang="ru"><surname>Корсакова</surname><given-names>Н. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Senior Research Fellow, Department of Pathological Anatomy</p></bio><bio xml:lang="ru"><p>канд. мед. наук, ст. науч. сотр. патологоанатомического отделения</p></bio><email>larisgur@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Voronkova</surname><given-names>I. A.</given-names></name><name xml:lang="ru"><surname>Воронкова</surname><given-names>И. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Physician, Laboratory of Pathomorphology</p></bio><bio xml:lang="ru"><p>канд. мед. наук, врач лаборатории фундаментальной патоморфологии</p></bio><email>larisgur@mail.ru</email><xref ref-type="aff" rid="aff3"/><xref ref-type="aff" rid="aff4"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kazantseva</surname><given-names>I. A.</given-names></name><name xml:lang="ru"><surname>Казанцева</surname><given-names>И. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Head of Department of Pathological Anatomy</p></bio><bio xml:lang="ru"><p>д-р мед. наук, руководитель патологоанатомического отделения</p></bio><email>larisgur@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Ashevskaya</surname><given-names>V. E.</given-names></name><name xml:lang="ru"><surname>Ашевская</surname><given-names>В. Е.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, Research Fellow, Department of Pathological Anatomy</p></bio><bio xml:lang="ru"><p>науч. сотр. патологоанатомического отделения</p></bio><email>larisgur@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Titov</surname><given-names>A. G.</given-names></name><name xml:lang="ru"><surname>Титов</surname><given-names>А. Г.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Leading Research Fellow, Department of Thoracic Surgery</p></bio><bio xml:lang="ru"><p>канд. мед. наук, вед. науч. сотр. хирургического торакального отделения</p></bio><email>larisgur@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Kogoniya</surname><given-names>L. M.</given-names></name><name xml:lang="ru"><surname>Когония</surname><given-names>Л. М.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Professor of Chair of Oncology and Thoracic Surgery, Postgraduate Training Faculty</p></bio><bio xml:lang="ru"><p>д-р мед. наук, профессор кафедры онкологии и торакальной хирургии факультета усовершенствования врачей</p></bio><email>larisgur@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Mazurin</surname><given-names>V. S.</given-names></name><name xml:lang="ru"><surname>Мазурин</surname><given-names>В. С.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Professor, Head of Department of Thoracic Surgery</p></bio><bio xml:lang="ru"><p>д-р мед. наук, профессор, руководитель хирургического торакального отделения</p></bio><email>larisgur@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Shabarov</surname><given-names>V. L.</given-names></name><name xml:lang="ru"><surname>Шабаров</surname><given-names>В. Л.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, Physician, Department of Thoracic Surgery</p></bio><bio xml:lang="ru"><p>канд. мед. наук, врач хирургического торакального отделения</p></bio><email>larisgur@mail.ru</email><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff2"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Moscow Regional Research and Clinical Institute (MONIKI)</institution></aff><aff><institution xml:lang="ru">ГБУЗ МО «Московский областной научно-исследовательский клинический институт им. М.Ф. Владимирского»</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">61/2 Shchepkina ul., Moscow, 129110, Russian Federation</institution></aff><aff><institution xml:lang="ru">129110, г. Москва, ул. Щепкина, 61/2, Российская Федерация</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">Endocrinology Research Center</institution></aff><aff><institution xml:lang="ru">ФБГУ «Эндокринологический научный центр» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff4"><aff><institution xml:lang="en">11 Dmitriya Ul'yanova ul., Moscow, 117036, Russian Federation</institution></aff><aff><institution xml:lang="ru">117036, г. Москва, ул. Дмитрия Ульянова, 11, Российская Федерация</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2016-08-15" publication-format="electronic"><day>15</day><month>08</month><year>2016</year></pub-date><volume>44</volume><issue>5</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>613</fpage><lpage>623</lpage><history><date date-type="received" iso-8601-date="2017-01-03"><day>03</day><month>01</month><year>2017</year></date><date date-type="accepted" iso-8601-date="2017-01-03"><day>03</day><month>01</month><year>2017</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2016, Gurevich L.E., Korsakova N.A., Voronkova I.A., Kazantseva I.A., Ashevskaya V.E., Titov A.G., Kogoniya L.M., Mazurin V.S., Shabarov V.L.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2016, Гуревич Л.Е., Корсакова Н.А., Воронкова И.А., Казанцева И.А., Ашевская В.Е., Титов А.Г., Когония Л.М., Мазурин В.С., Шабаров В.Л.</copyright-statement><copyright-year>2016</copyright-year><copyright-holder xml:lang="en">Gurevich L.E., Korsakova N.A., Voronkova I.A., Kazantseva I.A., Ashevskaya V.E., Titov A.G., Kogoniya L.M., Mazurin V.S., Shabarov V.L.</copyright-holder><copyright-holder xml:lang="ru">Гуревич Л.Е., Корсакова Н.А., Воронкова И.А., Казанцева И.А., Ашевская В.Е., Титов А.Г., Когония Л.М., Мазурин В.С., Шабаров В.Л.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://almclinmed.ru/jour/article/view/451">https://almclinmed.ru/jour/article/view/451</self-uri><abstract xml:lang="en"><p>Background: Neuroendocrine tumors of the lung (NETL) are a wide range of tumors with various malignancy grades and prognosis. Despite their prevalence being 20 to 25% of all lung cancers, many aspects that impact their clinical course and prognosis are not well understood. Aim  – to identify morphological and immunophenotypic characteristics of various NETL types would that more accurately reflect their biological potential and allow for prediction of their unfavorable clinical outcomes. Materials and methods: We performed immunohistochemical assessment of the diagnostic biopsies and surgical specimens from 152 patients with NETL aged 53 ± 13 years and identified 49  typical carcinoids, 32 atypical carcinoids, 60  small cell neuroendocrine carcinomas and 11  large cell neuroendocrine carcinomas, which accounted for 32.2, 21.1, 39.5 and 7.2%, respectively. Markers of neuroendocrine differentiation, such as synaptophysin, chromogranin A  and CD56, as well as cytokeratins 7 and 19, thyroid transcription factor-1 (TTF-1), and Ki67 were used. The results were analyzed with analysis of variance (ANOVA), chi-square test (χ²), and post-hoc comparisons with the Bonferroni correction. Results: Most often, the expression of cytokeratins 7 and 19 was found in large cell neuroendocrine carcinoma (72.7 and 90.9%, respectively), less frequently, in atypical carcinoids and small cell neuroendocrine carcinomas (50 and 53.3%; 41.7 and 64.6% of cases, respectively), whereas in typical carcinoids it was rare (5.9 and 15.9%, respectively). The rates of cytokeratin 7 and 19 expression were significantly lower in the typical carcinoids, compared to the atypical carcinoids, small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas (р &lt; 0.05, χ²). The expression of cytokeratin 19 was significantly more common for large cell neuroendocrine carcinomas, than for small cell neuroendocrine carcinomas and atypical carcinoids (р &lt; 0.01, χ²). The expression of TTF-1 was very rare in the typical carcinoid cells (6.5% of cases) and significantly more often in atypical carcinoids (61.5%) and in small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas (82.7 and 77.8% of cases, respectively). TTF-1 expression was significantly less frequent in typical than in atypical carcinoids, small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas (р &lt; 0.01, χ²). The mean index of tumor cell proliferation (Ki67) was the lowest in typical carcinoids (2.6%), amounted to 12% in atypical carcinoids, to 44% in large cell neuroendocrine carcinomas and reached the maximum of 61% in small cell neuroendocrine carcinomas. There were significant differences in the mean Ki67 index in the NETL 4 groups (р &lt; 0.001, ANOVA). Conclusion: Expression of TTF-1, cytokeratin 7 and 19 in the neuroendocrine tumors of the lung is characteristic for a  less differentiated cell immunophenotype and allows for identification of the risk group with unfavorable clinical outcome among low-grade typical and atypical carcinoids.</p></abstract><trans-abstract xml:lang="ru"><p>Актуальность. Нейроэндокринные опухоли легких (НЭОЛ) представляют собой целый спектр опухолей, различающихся по степени злокачественности и  прогнозу. Несмотря на их распространенность  – от  20 до 25% всех случаев рака данной локализации – многие аспекты, определяющие особенности клинического течения НЭОЛ и прогноз, еще недостаточно хорошо изучены. Цель  – выявить морфологические и  иммунофенотипические особенности разных типов НЭОЛ, которые бы более точно отражали их биологический потенциал и  позволяли прогнозировать менее благоприятное клиническое течение. Материал и  методы. Проводили иммуногистохимическое исследование диагностических биопсий и операционного материала от 152 пациентов с НЭОЛ в возрасте 53±13 лет. Были диагностированы 49 типичных карциноидов, 32 атипичных карциноида, 60 мелкоклеточных нейроэндокринных карцином/раков и  11 крупноклеточных нейроэндокринных карцином/раков, которые составили 32,2, 21,1, 39,5 и  7,2% соответственно. Использовали маркеры нейроэндокринной дифференцировки  – синаптофизин, хромогранин А  и  CD56, а  также цитокератины  7 и  19, тиреоидный фактор транскрипции-1 (TTF-1), Ki67. Pезультаты подвергли статистической обработке с  использованием дисперсионного анализа (ANOVA), критерия χ², апостериорных сравнений с  поправкой Бонферрони. Результаты. Чаще всего экспрессия цито- кератинов 7 и 19 встречалась в группе крупноклеточной нейроэндокринной карциномы – в 72,7 и 90,9% случаев соответственно, реже в  группе атипичного карциноида (50 и  53,3%) и  мелкоклеточной нейроэндокринной карциномы (41,7 и 64,6%), редко – типичного карциноида (5,9 и 15,9%). Частота экспрессии цитокератинов 7 и  19 была статистически значимо меньше в  группе типичного карциноида по сравнению с  атипичным карциноидом, мелкоклеточной и  крупноклеточной нейроэндокринными карциномами (р&lt;0,05, χ²,&gt; &lt;0,05, χ², апостериорные сравнения). Экспрессия цитокератина  19 значимо чаще наблюдалась в крупноклеточных нейроэндокринных карциномах, чем в мелкоклеточных нейроэндокринных карциномах и атипичных карциноидах (р &lt;0,05 χ², апостериорные сравнения). Экспрессия TTF-1 в  клетках типичных карциноидов выявлялась очень редко – в 6,5% случаев, в атипичных карциноидах значительно чаще  – в  61,5%, а  в мелкоклеточных и  крупноклеточных нейроэндокринных карциномах  – в  подавляющем большинстве случаев: 82,7 и  77,8% соответственно. Частота экспрессии TTF-1 в  типичных карциноидах была значимо меньше, чем в  атипичных карциноидах, мелкоклеточных и  крупноклеточных нейроэндокринных карциномах (р &lt;0,01, χ², апостериорные сравнения). Средний индекс пролиферации опухолевых клеток Ki67 был самым низким в  группе типичного карциноида  – 2,6%, в  группе атипичного карциноида он достигал 12%, крупноклеточной нейроэндокринной карциномы  – 44%, а  максимальным оказался при мелкоклеточной нейроэндокринной карциноме – 61%. Имелись статистически значимые различия в величине среднего индекса Ki67 во всех 4 группах НЭОЛ (р &lt;0,001, ANOVA, апостериорные сравнения). Заключение. Экспрессия в нейроэндокринных опухолях легкого TTF-1, цитокератинов 7 и 19 характеризует менее дифференцированный клеточный иммунофенотип и  позволяет выделить среди высокодифференцированных типичных и атипичных карциноидов группу риска с менее благоприятным клиническим течением. </p></trans-abstract><kwd-group xml:lang="en"><kwd>neuroendocrine tumors of the lung</kwd><kwd>Grade</kwd><kwd>prognostic factors</kwd><kwd>cytokeratin 7 expression</kwd><kwd>cytokeratin 19 expression</kwd><kwd>TTF-1</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>нейроэндокринные опухоли легких</kwd><kwd>Grade</kwd><kwd>факторы прогноза</kwd><kwd>экспрессия цитокератинов 7, 19</kwd><kwd>TTF-1</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>1. Travis WD, Brambilla E, Burke AP, Marx A, Nichol-son AG, editors. WHO Classiﬁcation of tumours of the lung, pleura, thymus and heart. 4th ed. 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