The axillary lymph node status remains the most valuable prognostic factor for
breast cancer patients. However, approximately 20-30% of node-positive patients remain free of distant
metastases within 15-30 years. It is important to develop molecular markers that are able to predict for the risk of distant
metastasis and to develop patient-tailored
therapy strategies. We hypothesize that the
lymph node metastases may represent the most metastatic fraction of the primary
cancers. Therefore, we sought to identify the differentially expressed genes by microarray between the primary
tumors and their paired
lymph node metastases samples collected from 26 patients. A set of 79 differentially expressed genes between primary
cancers and
metastasis samples was identified to correctly separate most of primary
cancers from
lymph node metastases. And decreased expression of
matrix metalloproteinase 2,
fibronectin, osteoblast specific factor 2,
collagen type XI alpha 1 in
lymph node metastases were further confirmed by real-time RT-PCR performed on 30 specimen pairs. This set of genes also classified 35 primary
cancers into two groups with different prognosis: "high risk group" and "low risk group." Patients in "high risk group" had a 4.65-fold hazard ratio (95% CI 1.02-21.13, P = 0.047) to develop a distant
metastasis within 43 months comparing with the "low risk group." This suggested that the gene signature consisting of 79 differentially expressed genes between primary
cancers and
lymph node metastases could also predict clinical outcome of node-positive patients, and that the molecular classification based on the gene signature could guide patient-tailored
therapy.