mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-AAT-2598mimmun-2598Research ArticleКРАТКИЕ СООБЩЕНИЯSHORT COMMUNICATIONSАнтиидиотипические антитела против эстрадиола и генетический полиморфизм эстрогеновых рецепторов α и β у больных раком молочной железыAntiidiotypic antibodies to estradiol and gene polymorphisms of α and β estrogenic receptors in breast cancer patientshttps://orcid.org/0000-0002-8560-6719ГлушковА. Н.GlushkovA. N.

Глушков Андрей Николаевич – д.м.н., профессор, главный научный сотрудник лаборатории иммуногенетики Института экологии человека 

г. Кемерово

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

Kemerovo

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

Поленок Елена Геннадьевна – к.фарм.н., ведущий научный сотрудник лаборатории иммунохимии Института экологии человека

г. Кемерово

Polenok Elena G., PhD (Pharmacy), Leading Research Associate, Immunochemistry Laboratory of Institute of Human Ecology

Kemerovo

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

Гордеева Людмила Александровна – к.б.н., ведущий научный сотрудник лаборатории иммуногенетики Института экологии человека 

г. Кемерово

Gordeeva Lyudmila A., PhD (Biology), Leading Research Associate, Immunogenetics Laboratory of Institute of Human Ecology

Kemerovo

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

Мун Стелла Андреевна – к.м.н., доцент, старший научный сотрудник лаборатории иммуногенетики Института экологии человека

Адрес для переписки:Мун Стелла Андреевна –Институт экологии человека ФГБНУ «Федеральный исследовательский центр угля и углехимии Сибирского отделения Российской академии наук»650065, Россия, г. Кемерово, Ленинградский пр., 10. Тел.: 8 (3842) 57-50-79.

Mun Stella A., PhD (Medicine), Associate Professor, Senior Research Associate, Immunogenetics Laboratory of Institute of Human Ecology

Address for correspondence:Stella A. Mun –Institute of Human Ecology, Federal Research Center of Coal and Coal Chemistry10 Leningradsky Ave Kemerovo650065 Russian FederationPhone: +7 (3842) 57-50-79.

stellamun@yandex.ruhttps://orcid.org/0000-0003-0802-9759АнтоновА. В.AntonovA. V.

Антонов Александр Витальевич – заведующий отделением опухолей молочной железы 

г. Кемерово

Antonov Alexander V., Head, Breast Cancer Department

Kemerovo

al0412@mail.ruБайрамовП. В.BayramovP. V.

Байрамов Павел Валерьевич – заведующий патологоанатомическим отделением

г. Кемерово

Bayramov Pavel V., Main Physician, Patholoanatomical Department

Kemerovo

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

Вержбицкая Наталья Евгеньевна – к.м.н., врач-патологоанатом 

г. Кемерово

Verzhbitskaya Natalia E., PhD (Medicine), Pathologist, Patholoanatomical Department

Kemerovo

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

Колпинский Глеб Иванович  – д.м.н., профессор кафедры лучевой диагностики, лучевой терапии и онкологии, Кемеровский государственный медицинский университет; главный врач, Клинический консультативно-диагностический центр имени И.А. Колпинского

г. Кемерово

Kolpinskiy Gleb I., PhD, MD (Medicine), Professor, Department of Radiology, Radiotherapy and Oncology, Kemerovo State Medical University; Main Physician, Kemerovo Clinical Diagnostic Сenter

Kemerovo

Glebss@mail.ruВафинИ. А.VafinI. A.

Вафин Илгиз Ахматович – главный врач 

г. Кемерово

 

Vafin Ilgiz A., Main Physician 

Kemerovo

gkuz.kots@yandex.ruФГБНУ «Федеральный исследовательский центр угля и углехимии Сибирского отделения Российской академии наук»РоссияFederal Research Center of Coal and Coal Chemistry, Siberian Branch, Russian Academy of SciencesRussian FederationГБУЗ «Кузбасский клинический онкологический диспансер имени М.С. Раппопорта»РоссияKuzbass Clinical Oncology DispensaryRussian FederationФГБОУ ВО «Кемеровский государственный медицинский университет»; ГАУЗ «Клинический консультативно-диагностический центр имени И.А. Колпинского»РоссияKemerovo State Medical University; Kemerovo Clinical Diagnostic СenterRussian FederationГКУЗ «Кузбасский центр крови»РоссияKuzbass Center of BloodRussian Federation202412092023261159168Copyright © Глушков А.Н., Поленок Е.Г., Гордеева Л.А., Мун С.А., Антонов А.В., Байрамов П.В., Вержбицкая Н.Е., Колпинский Г.И., Вафин И.А., 20242024Глушков А.Н., Поленок Е.Г., Гордеева Л.А., Мун С.А., Антонов А.В., Байрамов П.В., Вержбицкая Н.Е., Колпинский Г.И., Вафин И.А.Glushkov A.N., Polenok E.G., Gordeeva L.A., Mun S.A., Antonov A.V., Bayramov P.V., Verzhbitskaya N.E., Kolpinskiy G.I., Vafin I.A.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/2598

Markers for identification of ER+/PR+ breast cancer (BC) risks and conversion of ER+/ER+ to ER-/PR- tumors are necessary for effective prevention and therapy of BC by the selective ER modifying drugs. Our purpose was to reveal the suggested associations of gene polymorphisms of ESR1 and ESR2 and antiidiotypic antibodies to estradiol (IgG2-E2) with ER+/PR+ BC risk, and conversion of ER+/PR+ to ER-/PR- tumors and to study interrelations between gene variants of ESR and IgG2-E2 in healthy women and BC patients. Polymorphic loci of ESR1 (rs2234693) and ESR2 (rs4986938) were studied by the real-time PCR in 370 healthy women and 1169 BC patients. ER and PR in the tumor tissues were detected by standard immunohistochemical techniques. Serum IgG2-E2 were studied using non-competitive enzyme immunoassay. TT, TC and CC genotypes of ESR1 were revealed at the equal frequency in healthy women and stage I BC patients. GG homozygotes of ESR2 were detected rarely, but AA were more frequent in BC patients with ER+/PR+ tumors (stage I) than in healthy women (44.0% and 14.2% vs 52.7% and 8.4%, respectively; p = 0.005). Low levels of IgG2-ES were revealed more rarely but high levels were detected more frequently in BC patients with ER+/PR+ tumors (stage I) than in healthy persons (39.8% vs 60.2%, and 58.0% vs 42.0%, respectively; p = 0.0002). Decreasing proportion of ER+/PR+ tumors and corresponding increase of ER-/PR- tumors from stage I to II–IV (71.7% to 58.9% and 13.9% to 23.1%; p = 0.006) were revealed only for the TC heterozygotes of ESR1. The same conversion of ER+/PR+ tumors to ER-/PR- was detected for the GG homozygotes of ESR2 (p = 0.004). A similar ER/PR changes were revealed in BC patients with high IgG2-E2 levels (74.7% to 57.6% and 11.3%, to 25.0%, respectively, p < 0.0001). High and low IgG2-E2 levels showed similar frequency at any genotypes of ESR1 and ESR2, either among healthy women, or in BC patients. ESR1-2 gene polymorphisms and serum IgG2-E2 levels may be used as independent markers for prediction of ER+/PR+ breast cancer, and for assessment of ER+/PR+ to ER-/PR- tumor conversion during BC progression.

Markers for identification of ER+/PR breast cancer (BC) risks and conversion of ER+/ER+ to ER-/PR- tumors are necessary for effective prevention and therapy of BC by the selective ER – modificators. Purpose – To reveal the proposed associations of gene polymorphisms of   ESR1 and ESR2 and antiidiotypic antibodies to estradiol (IgG2-E2) with ER+/PR+ BC risk and conversion of ER+/PR+ to ER-/PR- tumors and to study the interrelations between gene variants of ESR and IgG2-E2 in healthy women and BC patients. Polymorphic loci of ESR1 (rs2234693) and ESR2 (rs4986938) were studied by the real time PCR in 370 healthy women and 1169 BC patients. Tumor tissues ER and PR were detected by the standard immunohistochemical methods. Serum IgG2-E2 were studied using non-competitive enzyme immuno-assay. TT, TC and CC genotypes of ESR1 were revealed with the equal frequency in healthy women and BC patients I stage. Homozygotes GG of ESR2 were detected rarely, but AA frequently in BC patients with ER+/PR+ tumors at the I stage, than in healthy women женщин (44.0% and 14.2% vs 52.7 and 8.4%, respectively; p=0.005). The low levels of IgG2-ES were revealed more rarely but high levels more frequently in BC patients with ER+/PR+ tumors at the I stage, that in healthy donors (39.8% and 60.2% vs 58.0% and 42.0%, respectively; p=0.0002). Decreasing of ER+/PR+ tumors proportion and corresponding increasing of ER-/PR- tumors from I stage to II–IV stages (71.7% to 58.9% and 13.9% to 23.1%; p=0.006) were revealed in TC heterozygotes of ESR1 only. The same conversion of ER+/PR+ tumors to ER-/PR- were detected in GG homozygotes of   ESR2 (p=0.004). There have been the similar ER/PR transformation in BC patients with high IgG2-E2 levels (74.7% to 57.6% and 11.3%, to 25.0%, respectively, p<0.0001). High and low IgG2-E2 levels were detected with the same proportions at the any genotypes of ESR1 and ESR2 in healthy women or in BC patients. ESR1-2 gene polymorphisms and serum IgG2-E2 levels may be used as independent markers for prediction of ER+/PR+ and for ER+/PR+ to ER-/PR- tumors conversion during BC progression.

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