Triple-negative, basal marker-expressing, and high-grade breast carcinomas are characterized by high lymphatic vessel density and the expression of podoplanin in stromal fibroblasts.

Abstract

Podoplanin, expressed in the lymphatic but not in the blood vessel endothelium, is widely used as a specific marker for lymphatic endothelial cells and lymphangiogenesis. The relation between lymphatic vessel density and breast cancer subtype or the expression of basal markers has not yet been investigated. We assessed lymphatic vessel density (LVD), blood vessel density, and the expression of podoplanin in stromal cancer-associated fibroblasts, in 156 invasive ductal breast cancers (T≥1, N≥1, M0). Afterwards, we assessed the relationship between the above-mentioned parameters and (i) breast cancer subtype (luminal vs. HER2 vs. triple negative), (ii) tumor grade (G1 vs. G2 vs. G3), (iii) the expression of cytokeratin (CK) 5/6, (iv) P-cadherin, (v) smooth muscle actin (SMA), and (vi) the pattern/intensity of stromal lymphocytic infiltration. We found a significantly higher LVD and podoplanin expression in stromal fibroblasts in (i) G3 tumors, (ii) triple-negative carcinomas, (iii) tumors expressing CK5/6, SMA, or P-cadherin, and (iv) neoplasms with stroma intensively infiltrated by lymphocytes. Moreover, we observed a significant inverse relationship between the expression of podoplanin in luminal A subtype, P-cadherin, CK5/6, and SMA-negative tumors and tumors without strong lymphocytic infiltration. A significantly higher percentage of tumors with strong lymphocytic infiltration was noted among G3 carcinomas. Breast carcinomas of different grades, subtypes, and basal marker expression are characterized by different composition of the stroma, that is different LVD, podoplanin expression in stromal fibroblasts, and the pattern/intensity of lymphocytic infiltration.