sibmedСибирский научный медицинский журналСибирский научный медицинский журнал2410-25122410-2520ИЦиГ СО РАН10.15372/SSMJ20190508sibmed-277Research ArticleМЕДИКО-БИОЛОГИЧЕСКИЕ НАУКИBIOMEDICINEСОПОСТАВИТЕЛЬНЫЙ АНАЛИЗ МОЛЕКУЛЯРНО-ГЕНЕТИЧЕСКИХ ХАРАКТЕРИСТИК ПЕРВИЧНОГО ОПУХОЛЕВОГО ОЧАГА И МЕТАСТАТИЧЕСКИХ ЛИМФАТИЧЕСКИХ УЗЛОВ ПРИ РАКЕ МОЛОЧНОЙ ЖЕЛЕЗЫMOLECULAR-GENETIC CHARACTERISTICS OF PRIMARY TUMOR AND METASTATIC LYMPHATIC NODES IN BREAST CANCERБоженкоВ. К.BozhenkoV. K.

д.м.н., проф., 

117997, г .Москва, ул. Профсоюзная, 86

doctor of medical sciences, professor

117997, Moscow, Profsoyuznaya str., 86

vbojenko@mail.ruТроценкоИ. Д.TrotsenkoI. D.

д.м.н.,

117198, г. Москва, ул. Миклухо-Маклая, 6

doctor of medical sciences

117198, Moscow, Mikluho-Maklay str., 6

trotsenkoivan@mail.ruКудиноваЕ. А.KudinovaE. A.

д.м.н., 

117997, г .Москва, ул. Профсоюзная, 86

doctor of medical sciences

117997, Moscow, Profsoyuznaya str., 86

dockudinova@mail.ruВарданянС. Г.VardanyanS. G.

8-916-302-31-31

117997, г .Москва, ул. Профсоюзная, 86

117997, Moscow, Profsoyuznaya str., 86

Bimmer007@list.ruЗахаренкоМ. В.ZakharenkoM. V.

117997, г .Москва, ул. Профсоюзная, 86

117997, Moscow, Profsoyuznaya str., 86

zak-margarita@mail.ruСолодкийВ. А.SolodkiyV. A.

д.м.н., проф., академик РАН,

117997, г .Москва, ул. Профсоюзная, 86

doctor of medical sciences, professor, academician of RAS

117997, Moscow, Profsoyuznaya str., 86

mailbox@rncrr.rssi.ruМакароваМ. В.MakarovaM. V.

117198, г. Москва, ул. Миклухо-Маклая, 6

117198, Moscow, Mikluho-Maklay str., 6

117997, Moscow, Profsoyuznaya str., 86

Российский научный центр рентгенорадиологии Минздрава РоссииРоссияRussian Scientific Center of Roentgenoradiology of Minzdrav of RussiaRussian FederationРоссийский университет дружбы народовРоссияUniversity of Peoples’ FriendshipRussian Federation2019021120193956875Copyright © Боженко В.К., Троценко И.Д., Кудинова Е.А., Варданян С.Г., Захаренко М.В., Солодкий В.А., Макарова М.В., 20192019Боженко В.К., Троценко И.Д., Кудинова Е.А., Варданян С.Г., Захаренко М.В., Солодкий В.А., Макарова М.В.Bozhenko V.K., Trotsenko I.D., Kudinova E.A., Vardanyan S.G., Zakharenko M.V., Solodkiy V.A., Makarova M.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://sibmed.elpub.ru/jour/article/view/277

Назначение системного лечения у больных раком молочной железы (РМЖ) основано в большей степени на молекулярных характеристиках первичной опухоли, однако многие клинические рекомендации предлагают исследование также метастатических очагов с оценкой их рецепторного статуса (рецепторов эстрогена (РЭ), рецепторов прогестерона (РП), рецепторов эпидермального фактора роста человека Her2/neu). Это обусловлено тем, что по данным многочисленных исследований несоответствие статуса первичной опухоли и вторичных узлов может достигать высоких показателей: 3–54 % для РЭ, 5–78 % для РП и 0–34 % для Her2/neu. В то же время все больше данных свидетельствуют о несовершенстве иммуногистохимического анализа и необходимости изучения дополнительных параметров для повышения качества диагностики больных РМЖ. Материал и методы. Выполнялось морфологическое и иммуногистохимическое изучение опухолевой ткани первичного узла и аксиллярных лимфатических узлов у 199 больных РМЖ (T1-3N0-3M0) по стандартным методикам, также проводилось исследование методом ПЦР с обратной транскрипцией с выявлением экспрессии 24 генов. Результаты. Частота различий молекулярных фенотипов основного опухолевого и пораженных аксиллярных лимфатических узлов составила 26 (26 %) из 99 случаев. Наиболее часто различия отмечались в случаях РМЖ с люминальным типом А – 13 случаев (50 %). По результатам сравнительного ПЦР-анализа опухолевой ткани основного опухолевого узла и пораженных регионарных лимфатических узлов статистически значимыми являлась лишь экспрессия рецепторов CD68, ERSR1, GRB7 и MMD11. Заключение. Полученные результаты свидетельствуют о необходимости комплексного подхода и проведения дополнительных методов диагностики РМЖ, что, несомненно, повысит качество планирования и эффективность системного лечения у больных РМЖ.

The purpose of systemic treatment in patients with breast cancer is based largely on the molecular characteristics of the primary tumor, but many clinical recommendations suggest also the study of metastatic nodes with an assessment of their receptor status (estrogen receptor ER, progesterone receptor RP, human epidermal growth factor receptor 2 Her2/neu). This is due to the fact that according to numerous studies, the discrepancy between the status of the primary tumor and the secondary nodes can reach high rates: 3–54 % for ER, 5–78 % for RP, and 0–34 % for Her2/neu. At the same time, more and more data actively demonstrate the imperfection of immunohistochemical analysis and the need to study additional parameters to improve the quality of diagnosis of patients with breast cancer. Material and methods. A morphological and immunohistochemical study of the tumor tissue of the primary node and axillary lymph nodes was performed in 199 patients with breast cancer (T1-3N0-3M0) using standard methods, and RT-PCR was also studied with the expression of 24 genes. Results. The incidence of differences between the molecular phenotypes of the main tumor and metastatic axillary lymph nodes was 26 (26 %) of 99 cases. Most often, differences were noted in cases of breast cancer with luminal A type – 13 cases (50 %). According to the results of a comparative PCR analysis of tissue samples from the primary tumor and metastatic regional lymph nodes, only the expression of the CD68, ERSR1, GRB7 and MMD11 receptors was statistically significant. Conclusion. The results indicate the need for an integrated approach and additional methods for the diagnosis of breast cancer, which will undoubtedly improve the quality of planning and the effectiveness of systemic treatment in patients with breast cancer.

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Cancer Inst. 2018; 110 (6): 568–580. doi: 10.1093/jnci/djx273.Timmer M., Werner J.M., Röhn G., Ortmann M., Blau T., Cramer C., Stavrinou P., Krischek B., Mallman P., Goldbrunner R. Discordance and conversion rates of progesterone-, estrogen-, and HER2/neu-receptor status in primary breast cancer and brain metastasis mainly triggered by hormone therapy. Anticancer Res. 2017; 37 (9): 4859–4865. doi: 10.21873/anticanres.11894.Timmer M., Werner J.M., Röhn G., Ortmann M., Blau T., Cramer C., Stavrinou P., Krischek B., Mallman P., Goldbrunner R. Discordance and conversion rates of progesterone-, estrogen-, and HER2/neu-receptor status in primary breast cancer and brain metastasis mainly triggered by hormone therapy. Anticancer Res. 2017; 37 (9): 4859–4865. doi: 10.21873/anticanres.11894.Timmer M., Werner J.M., Röhn G., Ortmann M., Blau T., Cramer C., Stavrinou P., Krischek B., Mallman P., Goldbrunner R. Discordance and conversion rates of progesterone-, estrogen-, and HER2/neu-receptor status in primary breast cancer and brain metastasis mainly triggered by hormone therapy. Anticancer Res. 2017; 37 (9): 4859–4865. doi: 10.21873/anticanres.11894.Timmer M., Werner J.M., Röhn G., Ortmann M., Blau T., Cramer C., Stavrinou P., Krischek B., Mallman P., Goldbrunner R. Discordance and conversion rates of progesterone-, estrogen-, and HER2/neu-receptor status in primary breast cancer and brain metastasis mainly triggered by hormone therapy. Anticancer Res. 2017; 37 (9): 4859–4865. doi: 10.21873/anticanres.11894.Untch M., Huober J., Jackisch C., Schneeweiss A., Brucker S.Y., Dall P., Denkert C., Fasching P.A., Fehm T., Gerber B., Janni W., Kühn T., Lüftner D., Möbus V., Müller V., Rody A., Sinn P., Thill M., Thomssen C., Harbeck N., Liedtke C. Initial treatment of patients with primary breast cancer: Evidence, controversies, consensus: spectrum of opinion of German specialists at the 15th international St. Gallen breast cancer conference (Vienna 2017). Geburtshilfe Frauenheilkd. 2017; 77 (6): 633–644. doi: 10.1055/s-0043-111601.Untch M., Huober J., Jackisch C., Schneeweiss A., Brucker S.Y., Dall P., Denkert C., Fasching P.A., Fehm T., Gerber B., Janni W., Kühn T., Lüftner D., Möbus V., Müller V., Rody A., Sinn P., Thill M., Thomssen C., Harbeck N., Liedtke C. Initial treatment of patients with primary breast cancer: Evidence, controversies, consensus: spectrum of opinion of German specialists at the 15th international St. Gallen breast cancer conference (Vienna 2017). 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The authors declare that there are no conflicts of interest present.