THE SIGNIFICANCE OF HOMING-ASSOCIATED PROTEIN EXPRESSION IN PROGRESSION OF LUMINAL SUBTYPE A BREAST CANCER

Iurchenko N.P., Nesina I.P., Chekhun V.F., Buchynska L.G.

• R.E. Kavetsky Institute of experimental pathology, oncology and radiobiology of NAS of Ukraine

Aim: to evaluate the expression of chemokine receptor CXCR4, its ligand — chemokine CXCL12, — mitochondrial ribosomal protein S18-2 and Кі-67 protein in tumor cells as well as the content of CD163⁺-macrophages in the stromal microenvironment of luminal A breast carcinomas of stage I-II. Object and methods: surgical samples of 55 patients with luminal A breast cancer (ВС) of stage I-II. The average age of patients was 58.4 ± 2.1 years. The study used clinical, morphological, immunohistochemical (IHC) and statistical methods. Results: In patients with luminal A BC, higher expression of CXCR4 and its ligand (64.7 ± 6.2 and 66.6 ± 5.1% respectively) was found in tumor cells of patients with stage I than in patients with stage II tumor process (47.5 ± 6.1 and 36.7% ± 6.4%, p <0.05, respectively). In addition, there were determined the differences in the expression of the studied markers in the group of patients with stage II BC depending on the presence or absence of metastases. An increase in the expression of CXCR4 (42.0 ± 10.2%), S18-2 (11.9 ± 1.7%), a decrease of CXCL12 (21.8 ± 7.6%) and the significantly greater number of cells expressing Ki-67 (23.1 ± 2.6%) were found in breast carcinomas of patients with metastases compared to those of patients with no metastases (respectively 33.9 ± 6.8 and 4.6 ± 0.8%; 54.3 ± 6.5%, (p <0.05) and 15.8 ± 2.2%,(p <0.05)). In the stromal component of breast carcinomas in patients with metastases a significantly higher content of CD163⁺-macrophages (17.5 ± 6.6%) was found compared to breast carcinomas of patients without metastatic lesions (5.6 ± 1.2%, p <0.05). The study demonstrated the heterogeneity of breast cancer in the expression of chemokine CXCL12, its receptor CXCR4, and the content of such immunosuppressive cells of the tumor environment as macrophages type 2 within one molecular subtype and one stage of the disease. Conclusions: in luminal A breast cancer, the intertumor heterogeneity of the expression of chemokine CXCL12, its receptor CXCR4, protein S18-2 in tumor cells, as well as of the content of CD163⁺-macrophages in the stromal microenvironment was shown. It was found that the lower expression of CXCL12, high CXCR4 and S18-2 in tumor cells together with the higher content of CD163⁺-macrophages in stromal microenvironment is associated with such signs of the tumor process aggressiveness as high proliferative potential, metastases in the lymph nodes and the obesity. The obtained data allow identifying more malignant breast cancer of luminal A subtype.