Lymphatic vessel density and its implications in breast cancer

Abstract

Introduction. Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death. Lymph node metastasis is one of the most important survival predictor in patients with cancers, this being crucial for tumor staging and therapy planning. Studies suggest that metastasizing is directly correlated with the density of lymphatic vessels in the tumor itself and in the peritumoral area.Aim of the study. The goal of our study was to study lymphatic vessels’ distribution (intratumoral vs peritumoral areas) as well as the relationships between tumor lymphangiogenesis and various parameters (such as hormone receptors and HER2 status, patients’ age, tumor grade). Materials and methods. We analyzed 84 cases of breast carcinomas in terms of their molecular profile and lymphatic vessels’ density determined in the intratumoral stroma (D2- 40it) and peritumoral area (D2-40pt), using the lymphatic endothelium marker D2-40. The relationships with different molecular subtypes of breast cancer and main clinical parameters were also analyzed. Results. Maximal values of both D2-40it and D2-40pt were achieved in case of triple- negative breast carcinomas (19 and 17, respectively). For luminal A, a positive correlation was detected between D2-40it and ER (r=0,611, p=0,012) and a negative correlation between D2-40pt and age (r=-0,533, p=0,033). D2-40pt positively correlated with D2-40it (r=0,676, p=0,011) in HER2+ subtype and in triple-negative breast carcinomas (r=0,631, p=0,028). D2-40pt negatively correlated with age in triple-negative subtype (r=-0,584, p=0,046). Analyzing overall molecular subtypes, we have found a positive correlation between D2-40it and tumor’s grade (r=0,289, p=0,008). Intratumoral lymphatic vessels’ amount negatively correlated with age (r=-0,242, p=0,026), hormone receptors ER (r=-0,339, p=0,002) and PR (r=-0,245, p=0,024). In G2 and G3 tumors, D2-40pt correlated with D2-40it (r=0,542, p=0,000069 and r=0,558, p=0,000206 respectively). In case of G3 tumors intratumoral lymphatic vessels negatively correlated with ER+ carcinoma cells (r=-0,406, p=0,016) and patients’ age (r=- 0,432, p=0,009). Conclusions. There are few data about interrelations between intratumoral and peritumoral lymphatic vessels in breast cancer. Intratumoral lymphatic vessel density is strongly influenced by the expression of hormone receptors. Our findings also suggest that lymphangiogenesis rate is higher in younger patients. The development of intratumoral and peritumoral lymphatic vessels is directly related.