Potential markers predicting distant metastasis in axillary node-negative breast carcinoma.

Prognostic parameters for axillary node-negative (ANN) breast cancer are still rare. Our aim was to establish potential markers that predict distant metastasis in ANN breast carcinoma and permit detection of the patients with high metastasis risk. A case control study was designed that comprised 64 ANN patients who developed distant metastasis during a 5-10 year follow-up period, 64 ANN patients with recurrence-free survival and 64 node-positive (ANP) comparitors. Immunohistochemistry and/or in situ hybridization were used to detect nm23, Cathepsin-D (Cath-D), Epidermal Growth Factor Receptor (EGFR) and Laminin Receptor (LR) in 192 cases. A significantly lower expression of both nm23 mRNA and protein was found in the ANN-group with poor prognosis compared with the ANN-group with good prognosis (p < 0.01). The protein levels of Cath-D, EGFR and LR were significantly higher in the ANN-group with poor prognosis and in the ANP-group compared with the ANN-group with good prognosis (p < 0.01 or p < 0.05), but no differences were found between the poor ANN-group and the ANP-group. Multiple regression analysis showed a close correlation of nm23, Cath-D and EGFR expression with occurrence of distant metastasis of ANN breast carcinoma. All markers except nm23 correlated with conventional histopathologic criteria such as tumor grade, margin and vessel invasion. The results suggest the combined detection of nm23, Cath-D and EGFR as predictive markers of distant metastasis in ANN breast cancer patients. Quantitative analysis together with clinicopathologic factors could contribute to estimate the potential risk of metastasis and select individual therapy regimen.