ANALYSIS OF ASSOCIATION BETWEEN THE DENSITY OF INFILTRATION IN PRIMARY CARCINOMA OF THE MAMMARY GLAND BY TUMOR-ASSOCIATED MACROPHAGES AND POSTOPERATIVE PROGNOSIS

  • A.Z. Aikian Ukrainian Medical Stomatological Academy, Poltava, Ukraine
  • V.I. Shynkevych Ukrainian Medical Stomatological Academy, Poltava, Ukraine
  • I.P. Kaidashev Ukrainian Medical Stomatological Academy, Poltava, Ukraine
Keywords: cancer / carcinoma of the mammary gland, tumor associated macrophages, molecular-biological types of. breast cancer, postoperative survival prediction

Abstract

Tumor-associated macrophages (TAM) of the M2-type dominate in tumors and produce molecules, favorable for their growth, stimulating tumor growth. However, changing the M2-type for M1 can slow down or arrest this growth. For realization of the M1 / M2 modulation direction in the treatment of carcinoma / breast cancer (BC), a substantiated diagnosis and confirmation of the TAM negative prognosis is necessary. Therefore, the aim of the study was to evaluate the relation of tumor associated macrophages to the postoperative prognosis / survival of patients with 5 molecular-biological types of breast carcinoma. Materials of the study were intraoperative tissues of tumors and ipsilateral lymph nodes in radically removed mammary glands. Pathomorphological study of lymph nodes was conducted to clarify the diagnosis in relation to N0/1. The density of TAM infiltration was determined by immunohistochemical staining of CD68 and CD163 in 30 samples of five molecular biological types of breast cancer (three clinical cases of each type). Immunohistochemical (IHC) studies for the determination of TAM and M2-like macrophages were conducted using streptavidin-peroxidase method. The quantitative representation of CD68 + and CD163 + Mph is very different from patient to patient and also within one sample, which depends, in particular, on the morphological characteristics of breast cancer, studied by the biopsy. The density of infiltration by CD163 + macrophages of the BC focus negatively correlated with postoperative survival, which did not reach statistical significance, but is included in the general concept of a negative prognosis of infiltration by M2-like macrophages. Further research is needed to confirm the negative significance of the ТАМ infiltration density in the BC primary focus for postoperative prognosis. Promising is the development of differential diagnosis and approach to the treatment of breast cancer, taking into account the levels of its infiltration by subpopulations of TAM.

Downloads

Download data is not yet available.

References

1. Mills CD, Lenz LL, Harris RA. A Breakthrough: Macrophage-Directed Cancer Immunotherapy. Cancer Res. 2016;76(3):513-6.
2. Zhao X, Qu J, Sun Y, Wang J, Liu X, Wang F et al. Prognostic significance of tumor-associated macrophages in breast cancer: a meta-analysis of the literature. 2017 May 2;8(18):30576-86.
3. Сharacteristics of cd68 + and cd163 + infiltration with macrophages of the primary focus and metastatic injuries of regional lymph nodes in luminal invasive carcinomas of the mammary gland depending on their immunophenotype. World of medicine and biology.2018;4(66):15-22..
4. Brady NJ, Chuntova P, Schwertfeger KL Macrophages: Regulators of the Inflammatory Microenvironment during Mammary Gland Development and Breast Cancer. Mediators Inflamm. 2016;4549676.
5. Buldakov M., Zavyalova M., Krakhmal N. et al. CD68+, but not stabilin-1+ tumor associated macrophages in gaps of ductal tumor structures negatively correlate with the lymphatic metastasis in human breast cancer. Immunobiology. 2015; 222(1):31-38/
6. Yang J, Li X, Liu X. The role of tumor-associated macrophages in breast carcinoma invasion and metastasis. Int J Clin Exp Pathol. 2015; 8(6):6656–64.
7. Mills CD, Thomas AC, Lenz LL, Munder M. Macrophage: SHIP of Immunity. Frontiers in Immunology. 2014;5:620.
8. Tashireva LA, Denisov EV, Gerashchenko TS, Pautova DN, Buldakov MA, Zavyalova MV et al. Intratumoral heterogeneity of macrophages and fibroblasts in breast cancer is associated with the morphological diversity of tumor cells and contributes to lymph node metastasis. 2017 Apr;222(4):631-40.
9. Medrek C, Pontén F, Jirström K, Leandersson K. The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients. BMC Cancer. 2012 Jul 23;12:306.
10. Movahedi K, Laoui D, Gysemans C, et al. Different tumor microenvironments contain functionally distinct subsets of macrophages derived from Ly6C(high) monocytes. Cancer Research. 2010;70(14):5728–39.
11. Ruffell B, Chang-Strachan D, Chan V, et al. Macrophage IL-10 blocks CD8+ T cell-dependent responses to chemotherapy by suppressing IL-12 expression in intratumoral dendritic cells. Cancer Cell. 2014;26(5):623–37.
Published
2019-04-12
How to Cite
Aikian, A., Shynkevych, V., & Kaidashev, I. (2019). ANALYSIS OF ASSOCIATION BETWEEN THE DENSITY OF INFILTRATION IN PRIMARY CARCINOMA OF THE MAMMARY GLAND BY TUMOR-ASSOCIATED MACROPHAGES AND POSTOPERATIVE PROGNOSIS. The Medical and Ecological Problems, 23(1-2), 3-7. https://doi.org/10.31718/mep.2019.23.1-2.01