The architecture of stroma is crucial for normal lymph node functioning, as well as for the systemic and local immune response. Data from previous studies in metastatic lymph nodes suggest that changes in the composition of extracellular matrix proteins may occur, not only around the lesion site, but throughout the lymph node stroma. In the present study, the extracellular matrix status was compared between the affected and metastasis-free lymph nodes in prostate cancer. It was found that the presence of tumor cells was associated with significant changes in the expression of genes encoding extracellular matrix components, including α4, β1 and γl laminin chains, osteonectin, and collagen, as well as with decrease in the expression of lymphatic endothelial cell biomarkers LYVE1 and NRP2. This result suggests that the normal stromal architecture is significantly disrupted in metastatic lymph nodes and may indicate the development of immune tolerance to the tumor cells.