Beschreibung:
<jats:p>Luminal B breast cancers (BC) have a more aggressive behavior associated with a higher rate of tumor relapse and worse prognosis compared to luminal A tumors. In this study, we evaluated the involvement of specific epithelial-to-mesenchymal transition- (EMT-) and immune-related pathways in the dissemination of luminal B BC cells. The expression of 42 EMT- and immune-related genes was evaluated in matched sentinel lymph nodes (SLNs) analyzed by the one-step nucleic acid amplification assay (OSNA) and primary tumors of 40 luminal B BC patients by gene array and immunohistochemistry. The results were validated in an independent group of 150 luminal B tumors by immunohistochemistry and immunofluorescence and using gene expression data from 315 luminal B BC patients included in the Metabric dataset. We found that the expression of <jats:italic>CXCR4</jats:italic> (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>3.28</mml:mn><mml:mi>E</mml:mi><mml:mo>−</mml:mo><mml:mn>02</mml:mn></mml:math>) and <jats:italic>CD163</jats:italic> (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>6.92</mml:mn><mml:mi>E</mml:mi><mml:mo>−</mml:mo><mml:mn>03</mml:mn></mml:math>) was significantly upregulated in SLNs of recurrent luminal B BC patients. Luminal B primary tumors overexpressing CXCR4 were characterized by an increased expression of vimentin and a high content of CD163-positive macrophages. Bioinformatics analysis confirmed the correlation of <jats:italic>CXCR4</jats:italic> with <jats:italic>CXCL12</jats:italic>, <jats:italic>VIM</jats:italic>, and <jats:italic>CD163</jats:italic> expression and LN involvement. Our results suggest that the upregulation of the CXCR4/CXCL12 pathway and the presence of protumor macrophages in the primary tumor and SLNs sustain the aggressiveness of an important subgroup of luminal B BC.</jats:p>