mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-IHP-3349mimmun-3349Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESИММУНО-ГОРМОНАЛЬНЫЕ ФЕНОТИПЫ, АССОЦИИРОВАННЫЕ С ПРОЛИФЕРАЦИЕЙ И МЕТАСТАЗИРОВАНИЕМ ОПУХОЛИ У БОЛЬНЫХ РАКОМ МОЛОЧНОЙ ЖЕЛЕЗЫImmuno-hormonal phenotypes associated with tumor proliferation and metastasis in breast cancer patientshttps://orcid.org/0000-0002-8560-6719ГлушковА. Н.GlushkovA. N.

д.м.н., профессор, главный научный сотрудник лаборатории иммуногенетики Института экологии человека 

PhD, MD (Medicine), Professor, Chief Research Associate, Immunogenetics Laboratory, Institute of Human Ecology

glushkovan@ihe.sbras.ruhttps://orcid.org/0000-0002-9368-2340ПоленокЕ. Г.PolenokE. G.

к.фарм.н.,  ведущий научный сотрудник лаборатории иммунохимии Института экологии человека

PhD (Pharmacy), Leading Research Associate, Immunochemistry Laboratory, Institute of Human Ecology

egpolenok@mail.ruhttps://orcid.org/0000-0001-5870-7584ГордееваЛ. А.GordeevaL. A.

к.б.н., ведущий научный сотрудник лаборатории иммуногенетики Института экологии человека 

PhD (Biology), Leading Research Associate, Immunogenetics Laboratory, Institute of Human Ecology

gorsib@rambler.ruhttps://orcid.org/0000-0002-5530-3469МунС. А.MunS. A.

к.м.н., старший научный сотрудник лаборатории иммуногенетики Института экологии человека 

PhD (Medicine), Senior Research Associate, Immunogenetics Laboratory, Institute of Human Ecology

stellamun@yandex.ruhttps://orcid.org/0000-0002-6623-8818СтуденниковА. Е.StudennikovA. E.

к.б.н., ведущий научный сотрудник лаборатории биотехнологии Института экологии человека 

PhD (Biology), Leading Research Associate, Biotechnology Laboratory, Institute of Human Ecology

StudennikovAE@ihe.sbras.ruhttps://orcid.org/0000-0003-2048-5888ГуровЕ. А.GurovE. A.

ведущий инженер-биолог лаборатории иммунохимии Института экологии человека 

Leading Engineer-Biologist, Immunochemistry Laboratory, Institute of Human Ecology

evgen4242@bk.ruhttps://orcid.org/0000-0003-0053-1752КостянкоМ. В.KostyankoM. V.

ведущий инженер кафедры фундаментальной и прикладной химии Института фундаментальных наук 

Leading Engineer, Fundamental and Applied Chemistry, Institute of Fundamental Sciences

kmvksu@mail.ruhttps://orcid.org/0009-0003-1731-1534ЗахаровВ. Н.ZakharovV. N.

главный врач 

Main Physician

vadim-zaxarov2016@ya.ruhttps://orcid.org/0000-0003-0802-9759АнтоновА. В.AntonovA. V.

заведующий отделением опухолей молочной железы 

Head, Breast Cancer Department

al0412@mail.ruhttps://orcid.org/0000-0002-4649-5892БайрамовП. В.BayramovP. V.

заведующий патологоанатомическим отделением 

Head, Pathologoanatomical Department

bayramov_pavel82@mail.ruhttps://orcid.org/0000-0003-3860-825XВержбицкаяН. Е.VerzhbitskayaN. E.

к.м.н., врач-патологоанатом 

PhD (Medicine), Pathologist

verzhbitskaja@mail.ruhttps://orcid.org/0000-0002-5526-2687КолпинскийГ. И.KolpinskyG. I.

профессор кафедры лучевой диагностики, лучевой терапии и онкологии;  главный врач 

PhD, MD (Medicine), Professor, Department of Radiology, Radiotherapy and Oncology; Main Physician

Glebss@mail.ruФГБНУ «Федеральный исследовательский центр угля и углехимии Сибирского отделения Российской академии наук», г. Кемерово, РоссияРоссияFederal Research Center for Coal and Coal Chemistry, Siberian Branch, Russian Academy of Sciences, Kemerovo, Russian FederationRussian FederationФГБОУ ВО «Кемеровский государственный университет», г. Кемерово, РоссияРоссияKemerovo State University, Kemerovo, Russian FederationRussian FederationГБУЗ «Кузбасский клинический онкологический диспансер им. М.С. Раппопорта», г. Кемерово, РоссияРоссияM. Rappoport Kuzbass Clinical Oncology Dispensary, Kemerovo, Russian FederationRussian FederationФГБОУ ВО «Кемеровский государственный медицинский университет» Министерства здравоохранения Российской Федерации, г. Кемерово, Россия; ГАУЗ «Клинический консультативно-диагностический центр им. И.А. Колпинского», г. Кемерово, РоссияRussian FederationKemerovo State Medical University, Kemerovo, Russian Federation; I. Kolpinsky Clinical Consultative and Diagnostic Сenter, Kemerovo, Russian FederationRussian Federation20190502202600Online First3349Copyright © Глушков А.Н., Поленок Е.Г., Гордеева Л.А., Мун С.А., Студенников А.Е., Гуров Е.А., Костянко М.В., Захаров В.Н., Антонов А.В., Байрамов П.В., Вержбицкая Н.Е., Колпинский Г.И., 20192019Глушков А.Н., Поленок Е.Г., Гордеева Л.А., Мун С.А., Студенников А.Е., Гуров Е.А., Костянко М.В., Захаров В.Н., Антонов А.В., Байрамов П.В., Вержбицкая Н.Е., Колпинский Г.И.Glushkov A.N., Polenok E.G., Gordeeva L.A., Mun S.A., Studennikov A.E., Gurov E.A., Kostyanko M.V., Zakharov V.N., Antonov A.V., Bayramov P.V., Verzhbitskaya N.E., Kolpinsky G.I.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/3349

Ранее были обнаружены взаимосвязи пролиферативной активности опухоли с уровнями антител против эстрадиола (E2) и прогестерона (Pg) (IgA1-E2 и IgA1-Pg, IgG1-E2 и IgG1-Pg) и соответствующих антиидиотипических антител (IgG2-E2 и IgG2-Pg) у больных раком молочной железы (РМЖ). Цель работы – исследовать комбинированное влияние E2 и Pg, антител против бензо[а]пирена (Bp), E2 и Pg, антиидиотипических антител к E2 и Pg на содержание в опухоли Ki67 положительных клеток в сочетании с метастазированием у больных РМЖ. Обследовали 620 женщин с I стадией РМЖ, 475 – со II и 150 – с III+IV стадиями до начала противоопухолевого лечения. Исследуемые антитела и анти-антитела анализировали с помощью ELISA, используя конъюгаты этих гаптенов с BSA и соответствующие моноклональные антитела в качестве адсорбированных антигенов. Искомые взаимосвязи исследовали у больных РМЖ со II стадией с помощью CART-анализа. Все больные разделились на группы с различными индивидуальными комбинациями уровней исследованных факторов. У 143 больных с IgG2-Pg ≤1,95 у.е. опухоли с низкой пролиферативной активностью и наличием метастазов (Ki67≤20% + Met+) встречались реже, а активно пролиферирующие без метастазов (Ki67>20% + Met-) чаще, чем у 332 больных с IgG2-Pg>1,95 у.е. (10,0% vs 21,1% и 42,0% vs 26,2%, p<0,01). У 94 больных с IgG2-Pg>1,95 у.е. в комбинации с IgG1-Bp>14,3 у.е. опухоли с Ki67>20% обнаруживали чаще, чем у 238 с IgG2-Pg>1,95 у.е. в комбинации с IgG1-Bp≤14,3 у.е. (69,2% vs 50,1%, p<0,01). У 102 больных с одновременно высокими IgG2-Pg>2,1 у.е. + IgG2-E2>3,3 у.е. опухоли с Ki67≤20% + Met- встречались чаще, а опухоли с Ki67>20% + Met+ реже, по сравнению с 42 больными, с повышенным содержанием только IgG2-Pg (33,3% и 16,7% vs 7,1% и 31,0%, p<0,01). 43 женщины с высокими E2>166 pmol/L (в комбинации с IgG2-Pg>2,1 у.е. + IgG1-Bp≤14,3 у.е. + Pg>869 pmol/L) имели наиболее агрессивные опухоли (Ki67>20% + Met+), чем 33 больных с E2≤166 pmol/L (55,8% vs 21,2%, p<0,01). Каждая из выделенных комбинаций антител и гормонов встречались с одинаковой частотой у больных с I, II и III+IV стадиями РМЖ. Таким образом, индивидуальные особенности пролиферации и метастазирования опухоли у больных РМЖ II стадии зависели от индивидуальных особенностей образования IgG2-Pg, IgG2-E2, IgG1-Bp, E2 и Pg. Иммуно-гормональные фенотипы не изменялись по мере роста опухоли.

Previously, the associations were described between tumor proliferation rates (levels of Ki67 positive cells), and levels of IgA and IgG antibodies against estradiol (E2) and progesterone (Pg) (IgA1-E2 and IgA1-Pg, IgG1-E2 and IgG1-Pg) as well as corresponding antiidiotypic antibodies (IgG2-E2 and IgG2-Pg) in breast cancer patients (BCP). The purpose of the present work was to look for a combined influence of E2 and Pg, antibodies against benzo[a]pyrene (Bp), E2 and Pg, and antiidiotypic antibodies to E2 and Pg, searching for relations with Ki67 positive cells in tumors and metastatic disease in BCP. We performed studies in blood serum of 1245 BC patients before anticancer treatment (620 women with stage I BCP; 475, stage II; 150, with stages III+IV). Antibodies and antiantibodies were studied using ELISA technique with adsorbed haptens-BSA conjugates and monoclonal antibodies to E2 and Pg, respectively. The patients were divided into several groups with different individual levels of the studied factors. Low-proliferating tumors (Ki67≤20%) combined with metastases (Met+) were less frequent whereas tumors with Ki67>20% + Met- were more common among 143 BCP with IgG2-Pg ≤1.95 conventional units (c.u.) than in 332 BCP with IgG2-Pg>1.95 c.u. (10.0% vs 21.1% and 42.0% vs 26.2%, p<0.01). Tumors with Ki67>20% were revealed in 94 BCP with IgG2-Pg>1.95 c.u. + IgG1-Bp>14.3 c.u., more frequently than in 238 BCP with IgG2-Pg >1.95 c.u. + IgG1-Bp≤ 4.3 c.u. (69.2% vs 50.1%, p<0.01). Tumors with Ki67≤20% + Met- were diagnosed more frequently, and Ki67>20% + Met+ were less common in 102 BCP with IgG2-Pg>2.1 c.u. + IgG2-E2>3.3 c.u. than in 42 BCP with IgG2-Pg>2.1 c.u. + IgG2-E2≤3.3 c.u. (33.3% and 16.7% vs 7.1% and 31.0%, p<0.01). 43 BCP had high levels of E2 (>166 pmol/L) combined with IgG2-Pg>2.1 c.u. + IgG1-Bp≤14.3 c.u. + Pg>869 pmol/L, and the most aggressive tumors (Ki67>20% + Met+) more frequent than 33 BCP with low levels of E2≤166 pmol/L combined with the same factors (55.8% vs 21.2%, p<0.01). Each of these immuno-hormonal phenotypes has been found equally common in BCP with I, II, and III+IV stages. In conclusion, individual features on the tumor proliferation and metastasis in II stage BCP were dependent on individual combinations of IgG2-Pg, IgG2-E2, IgG1-Bp, E2, and Pg serum levels. Immuno-hormonal phenotypes during tumor growth did not change upon tumor progression.

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The authors declare that there are no conflicts of interest present.