Abstract
Lymph node (LN) metastasis is an important prognostic parameter in breast carcinoma, a crucial site for tumour-immune cell interaction and a gateway for further dissemination of tumour cells to other metastatic sites. To gain insight into the underlying molecular changes from the pre-metastatic, via initial colonisation to the fully involved LN, we reviewed transcriptional research along the evolving microenvironment of LNs in human breast cancers patients. Gene expression studies were compiled and subjected to pathway-based analyses, with an emphasis on immune cell-related genes. Of 366 studies, 14 performed genome-wide gene expression comparisons and were divided into six clinical-biological scenarios capturing different stages of the metastatic pathway in the LN, as follows: metastatically involved LNs are compared to their patient-matched primary breast carcinomas (scenario 1) or the normal breast tissue (scenario 2). In scenario 3, uninvolved LNs were compared between LN-positive patients and LN-negative patients. Scenario 4 homed in on the residual uninvolved portion of involved LNs and compared it to the patient-matched uninvolved LNs. Scenario 5 contrasted uninvolved and involved LNs, whilst in scenario 6 involved (sentinel) LNs were assessed between patients with other either positive or negative LNs (non-sentinel).Gene lists from these chronological steps of LN metastasis indicated that gene patterns reflecting deficiencies in dendritic cells and hyper-proliferation of B cells parallel to tumour promoting pathways, including cell adhesion, extracellular matrix remodelling, cell motility and DNA repair, play key roles in the changing microenvironment of a pro-metastatic to a metastatically involved LN. Similarities between uninvolved LNs and the residual uninvolved portion of involved LNs hinted that LN alterations expose systemic tumour-related immune responses in breast cancer patients. Despite the diverse settings, gene expression patterns at different stages of metastatic colonisation in LNs were recognised and may provide potential avenues for clinical interventions to counteract disease progression for breast cancer patients.