Expression of macrophage-associated genes in breast tumors: relation to tumor progression

Background. Tumor-associated macrophages (TAM) are the main innate immunity cells that regulate the relationship between the infiltrating immunocompetent cells, tumor cells and other components of the microenvironment. TAMs can promote tumor cell proliferation and angiogenesis and can also contribute to tumor response to chemotherapy. The purpose of the study was to assess the prognostic significance of YKL39 and CCL18 gene expression in breast TAMs prior to treatment. Material and methods. A total of 96 patients with histologically verified invasive breast carcinoma of no special type (T1-4N0-3M0) were included into the study. The patients received 2-4 cycles of neoadjuvant chemotherapy. The 5-year metastasis-free survival was analyzed. The YKL39 and CCL18 expression levels were assessed using TaqMan real-time RTPCR. The expression level of >1 (higher than that in the normal tissue) indicated the gene overexpression. Results. There was no association between the YKL39 and CCL18 gene expression levels and the clinical and pathologic features. However, the levels of YKL39 and CCL18 gene expressions were significantly higher in patients having no distant metastases within a 5-year follow-up. Metastasis-free survival was estimated in patients with overexpression of YKL39 and CCL18 genes (YKL39+CCL18+ ) and in patients with low and high expression levels (YKL39-CCL18-, YKL39-CCL18+, YKL39+CCL18-) using the Kaplan-Meier method.All 100 % of patients (10 out of 10) with YKL39+CCL18+ macrophage phenotype in a tumor were alive and had no evidence of tumor progression during 5 years of follow-up. In patients with YKL39+CCL18- phenotype, the metastasis-free survival rate was 85 %. In patients with YKL39-CCL18+ and YKL39-CCL18- phenotypes, the 5-year survival rates were 71 % and 69 %, respectively. A statistically significant difference in metastasis-free survival between patients with YKL39+CCL18+ phenotype and YKL39-CCL18+ or YKL39-CCL18- phenotypes was found. Data obtained showed the association between TAM marker gene expression and metastasis free survival of breast cancer patients treated with NACT.