fcmedicineФундаментальная и клиническая медицинаFundamental and Clinical Medicine2500-07642542-0941КемГМУ10.23946/2500-0764-2022-7-1-53-63fcmedicine-515Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL RESEARCHАссоциации антител, специфичных к бензо[а]пирену, эстрадиолу и прогестерону, с эстрогеновыми рецепторами в опухолевой ткани при раке молочной железыAssociations of antibodies to benzo[a]pyrene, estradiol and progesterone with estrogen receptor phenotype in breast cancer tissuehttps://orcid.org/0000-0002-9368-2340ПоленокЕ. Г.PolenokE. G.

Поленок Елена Геннадьевна, кандидат фармацевтических наук, ведущий научный сотрудник лаборатории иммунохимии

650065, г. Кемерово, пр. Ленинградский, д. 10

Elena G. Polenok, PhD, Leading Researcher, Laboratory ofImmunochemistry

10, Leningradskiy Prospekt, Kemerovo, 650065

https://orcid.org/0000-0002-5530-3469МунС. А.MunS. A.

Мун Стелла Андреевна, кандидат медицинских наук, доцент,старший научный сотрудник лаборатории иммуногенетики

650065, г. Кемерово, пр. Ленинградский, д. 10

 

Stella A. Mun, MD, PhD, Senior Research Fellow, Laboratory ofImmunogenetics

10, Leningradskiy Prospekt, Kemerovo, 650065

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

Гордеева Людмила Александровна, кандидат биологическихнаук, ведущий научный сотрудник лаборатории иммуногенетики

650065, г. Кемерово, пр. Ленинградский, д. 10

Lyudmila A. Gordeeva, PhD, Leading Researcher, Laboratory ofImmunogenetics

10, Leningradskiy Prospekt, Kemerovo, 650065

https://orcid.org/0000-0003-0053-1752КостянкоМ. В.KostyankoM. V.

Костянко Михаил Владимирович, ведущий инженер кафедрыорганической химии

650000, г. Кемерово, ул. Красная, д. 6

Mikhail V. Kostyanko, Leading Engineer, Department of OrganicChemistry, Institute of Basic Science

6, Krasnaya Street, Kemerovo, 650000

https://orcid.org/0000-0003-0802-9759АнтоновА. В.AntonovA. V.

Антонов Александр Витальевич, заведующий онкологическим отделением №5

650036, г. Кемерово, ул. Волгоградская, д. 35

Alexander V. Antonov, MD, Head of the Oncology Unit №5

35, Volgogradskaya Street, Kemerovo, 650036

https://orcid.org/0000-0003-3860-825XВержбицкаяН. Е.VerzhbitskayaN. E.

Вержбицкая Наталья Евгеньевна, кандидат медицинских наук, заведующая патологоанатомическим отделением

650036, г. Кемерово, ул. Волгоградская, д. 35

Natalia E. Verzhbitskaya, MD, PhD, Head of the Pathology Unit

35, Volgogradskaya Street, Kemerovo, 650036

https://orcid.org/0000-0002-5526-2687КолпинскийГ. И.KolpinskiyG. I.

Колпинский Глеб Иванович, доктор медицинских наук, профессор кафедры лучевой диагностики и лучевой терапии с курсом онкологии; главный врач

650056, г. Кемерово, ул. Ворошилова, д. 22а;

650066, г. Кемерово, пр. Октябрьский, д. 53/1

Gleb I. Kolpinskiy, MD, DSc, Professor, Department of Radiology,Radiotherapy and Oncology; Head of Kemerovo

22a, Voroshilova Street, Kemerovo, 650056;

53/1, Oktyabrskiy Prospekt, Kemerovo, 650066

https://orcid.org/0000-0002-8560-6719ГлушковА. Н.GlushkovA. N.

Глушков Андрей Николаевич, доктор медицинских наук, профессор, главный научный сотрудник лаборатории иммуногенетики

650065, г. Кемерово, пр. Ленинградский, д. 10

Andrey N. Glushkov, MD, DSc, Professor, Chief Researcher,Laboratory of Immunogenetics

10, Leningradskiy Prospekt, Kemerovo, 650065

Институт экологии человека Федерального исследовательского центра угля и углехимии Сибирского отделения Российской академии наукРоссияInstitute of Human Ecology, Federal Research Center of Coal and Coal Chemistry within the Siberian Branch of the Russian Academy of SciencesRussian FederationФГБОУ ВО «Кемеровский государственный университет»РоссияKemerovo State UniversityRussian FederationГБУЗ «Кузбасский клинический онкологический диспансер»РоссияKuzbass Clinical Oncological DispensaryRussian FederationФГБОУ ВО «Кемеровский государственный медицинский университет» Министерства здравоохранения Российской Федерации; ГАУЗ «Клинический консультативно-диагностический центр»РоссияKemerovo State Medical University; Clinical Diagnostic CenterRussian Federation202231032022715363Copyright © Поленок Е.Г., Мун С.А., Гордеева Л.А., Костянко М.В., Антонов А.В., Вержбицкая Н.Е., Колпинский Г.И., Глушков А.Н., 20222022Поленок Е.Г., Мун С.А., Гордеева Л.А., Костянко М.В., Антонов А.В., Вержбицкая Н.Е., Колпинский Г.И., Глушков А.Н.Polenok E.G., Mun S.A., Gordeeva L.A., Kostyanko M.V., Antonov A.V., Verzhbitskaya N.E., Kolpinskiy G.I., Glushkov A.N.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://fcm.kemsmu.ru/jour/article/view/515Цель

Цель. Выявить предполагаемые ассоциации антител класса А, специфичных к бензо[а]пирену, эстрадиолу и прогестерону (IgA-Bp, IgA-Es, IgA-Pg), с конверсией эстроген-рецептор положительных (ER+) опухолей в эстроген-рецептор отрицательные (ER-) при прогрессии рака молочной железы.

Материалы и методы

Материалы и методы. Исследовали IgABp, IgA-Es и IgA-Pg в сыворотке крови 338 здоровых и 1407 больных раком молочной железы (I стадии – 564; II стадии – 595; III + IV стадий – 248) с помощью полуколичественного иммуноферментного анализа. Коньюгаты Bp, Es и Pg с бычьим сывороточным альбумином использовали в качестве адсорбированных антигенов и анти-IgA человека, меченые пероксидазой хрена – для проявления связавшихся специфических антител. Рассчитывали индивидуальные соотношения уровней исследуемых антител: IgA-Bp/IgA-Pg и IgA-Es/IgAPg. Наличие эстрогеновых рецепторов в ткани опухоли исследовали с помощью стандартного иммуногистохимического метода.

Результаты

Результаты. Низкие значения IgA-Bp/IgAPg≤1 в комбинации с низкими значениями IgAEs/IgA-Pg≤1 (протективный иммунологический фенотип) у здоровых женщин обнаруживали чаще, чем у больных раком молочной железы I стадии с ER+ и ER- опухолями (43,8% против 12,9% и 23,9%, p<0,0001 и p<0,001 соответственно). Высокие значения IgA-Bp/IgAPg>1 в комбинации IgA-Es/IgA-Pg>1 (проканцерогенный иммунологический фенотип) у здоровых женщин встречались реже, чем у больных раком молочной железы (27,5% против 65,5% и 58,7%, p<0,0001). Различия между больными раком молочной железы I стадии с ER+ и ER- опухолями по иммунологическим фенотипам оказались статистически достоверными (р = 0,017). Количество больных с ER+ опухолями на I стадии рака молочной железы (83,7%) было больше, а с ER- опухолями (16,3%) меньше, чем на II–IV стадиях (74,4% и 25,6%, p<0,0001). Конверсия ER+ опухолей в ER- при прогрессии заболевания оказалась характерна для пациенток с проканцерогенным иммунологическим фенотипом (p<0,0001), но не с протективным иммунологическим фенотипом (р>0,05).

Заключение

Заключение. Иммуноанализ антител против Bp, Es и Pg может быть использован для повышения эффективности селективных модуляторов эстрогеновых рецепторов в профилактике и лечении рака молочной железы.

Aim

Aim. To reveal the associations of IgA antibodies to benzo[a]pyrene, estradiol and progesterone (IgA-Bp, IgA-Es, IgA-Pg) with the conversion of estrogen-receptor positive (ER+) into estrogen-receptor negative (ER-) tumors during breast cancer progression.

Materials and Methods

Materials and Methods. Having collected serum samples from 338 healthy volunteers and 1407 breast cancer patients, we have profiled them for IgA-Bp, IgA-Es, IgA-Pg by means of enzyme-linked immunosorbent assay. Conjugates of bovine serum albumin with Bp, Es and Pg were used as adsorbed antigens and anti-human IgA horseradish peroxidase-conjugated antibodies were used for the detection of specific antigen-bound antibodies. Individual IgA-Bp/IgA-Pg and IgA-Es/IgA-Pg ratios were calculated. Estrogen receptor phenotype was determined using immunohistochemistry.

Results

Results. Low IgA-Bp/IgA-Pg ratios (≤ 1) in combination with low IgA-Es/IgA-Pg ratios (≤ 1) indicative of protective immunophenotype were more frequently revealed in healthy women (43.8%) in comparison with stage 1 breast cancer patients with ER+ (12.9%) and ER- (23.9%) tumors. High IgA-Bp/IgA-Pg ratios (>1) with high IgA-Es/IgA-Pg ratios (>1) suggestive of pro-carcinogenic immunological phenotype were less often detected in healthy women (27.5%) as compared with stage 1 breast cancer patients with ER+ (65.5%) and ER- (58.7%) tumors. Prevalence of protective and pro-carcinogenic phenotypes significantly differed in stage 1breast cancer patients with ER+ and ER- tumor phenotypes (p = 0.017). ER- tumor phenotype was more prevalent at II-IV tumor stages (25.6%) than at the stage 1 (16.3%). Conversion of ER+ to ER- tumors reflecting the breast cancer progression was characteristic for the patients with pro-carcinogenic immunological phenotype (p<0.0001).

Conclusion

Conclusion. Detection of antibodies against Bp, Es and Pg may be applied as a risk marker of breast cancer development and progression.

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