Relationship between the ratio of mesenchymal cells or macrophages to cancer cells in lymphovascular invasion and clinicopathologic features and prognosis of pT1-4N1-3M0 breast cancer patients

Objective To investigate the relationship between the ratio of mesenchymal cells to cancer cells or macrophages to cancer cells in lymphovascular invasion (LVI) and clinicopathologic features and prognosis of pT1-4N1-3M0 breast cancer patients. Methods A total of 167 pT1-4N1-3M0 breast cancer patients who received systemic treatment and had complete follow-up data in the First Affiliated Hospital of China Medical University, the First and Second Affiliated Hospitals of Dalian Medical University from January 2013 to December 2015 were enrolled in this retrospective study, with a median follow-up period of 55.2 months (16.8-69.6 months). Immunohistochemistry was used to identify the number of mesenchymal cells or macrophages in LVI. The ratio of mesenchymal cells to cancer cells and the ratio of macrophages to cancer cells in LVI were calculated. The Ward clustering method was used to divide the patients into two groups: high-ratio group and low-ratio group. Kruskal-Wallis H test and χ2 test were used to analyze the relationship between the ratios and clinicopathologic features of breast cancer patients; the log-rank test was used to analyze the relationship between the ratios and the patient prognosis. Results The ratios [M(P25-P75)] of mesenchymal cells to cancer cells and macrophages to cancer cells in 167 patients were 0.025 (0.015-0.063) and 0.023 (0.015-0.036), respectively. The ratio of mesenchymal cells to cancer cells was correlated with histological grade, tumor size, lymph node metastasis, clinical stage and LVI (χ2=10.210, 6.210, 64.315, 56.901, 19.771; P=0.001, 0.045, and all P<0.001), but not correlated with ER, PR, HER-2, Ki67 expression and nerve invasion (χ2=3.148, 2.260, 3.187, 0.145, 1.384; P=0.076, 0.133, 0.074, 0.704, 0.240). The ratio of macrophages to cancer cells was correlated with tumor size, ER expression, nerve invasion, histological grade, lymph node metastasis, clinical stage, LVI and HER-2 expression(χ2=7.487, 6.680, 8.439, 13.002, 25.856, 31.394, 19.771, 27.921; P=0.024, 0.010, 0.004, all P<0.001), but not correlated with Ki67 and PR expression (χ2=3.616, 1.183; P=0.057, 0.277). After clustering, the ratio of mesenchymal cells to cancer cells was related to lymph node metastasis and clinical stage (χ2=47.3, P<0.001; χ2=14.260, P=0.001); the ratio of macrophages to cancer cells was related to ER expression (χ2=5.136, P=0.023). The patients with a higher ratio of mesenchymal cells or macrophages to cancer cells in LVI had a lower DFS (worse prognosis) (χ2=24.124, 18.746, both P<0.001). Conclusion High ratio of mesenchymal cells or macrophages to cancer cells in LVI suggests poor prognosis, so the ratio could serve as an indicator for recurrence risk of pT1-4N1-3M0 breast cancer patients. Key words: Mesenchymal cells; Macrophages; Breast neoplasms; Survival rate; Prognosis; Lymphovascular invasion; Tumor microenvironment