THE RELATIONSHIP BETWEEN NM23, ANGIOGENESIS, AND THE METASTATIC PROCLIVITY OF NODE-NEGATIVE BREAST-CANCER

Distant metastases are the major cause of morbidity and mortality in w omen,vith breast cancer. The prediction of this metastatic proclivity is essential in determining prognosis and should allow an appropriate choice of therapy. A critical look at the metastatic process and its p henotypic expression offers an opportunity to identify some of the imp ortant events in the process that may relate to prognosis, with the go al of identifying those patients with occult metastases and also spari ng systemic treatment in those patients whose tumors have not develope d the capacity for distant spread. To evaluate the significance of nm2 3 and angiogenesis in the metastatic cascade, we used archival materia l from 163 node-negative breast cancer patients who had a median follo w-up of 14 years. All patients underwent mastectomy and received no ad juvant chemotherapy or hormone or radiation therapy. Immunohistochemis try was used to detect nm23-H1 expression, whereas angiogenesis was de termined by microvessel count (MVC). We found the 15-year disease-free survival (DFS) to be significantly better in patients with high nm23 compared with low nm23 (91% compared with 70%, P = 0.008). Low MVC is associated with excellent (92%) long-term DFS. In those patients with high MVC, high nm23 allows the identification of a subgroup with signi ficantly higher DFS (90% compared with 66%, P = 0.02). Among high nucl ear grade tumors, if nm23 is high, the DFS is significantly better (89 % compared with 68%, P = 0.03). Thus, nm23 is still associated with ex cellent survival, even when there is unfavorable angiogenesis or nucle ar grade. Multivariate analysis confirms that nm23 and MVC are importa nt prognostic factors. High MVC appears necessary but not sufficient f or metastasis to occur, whereas low nm23 may further contribute to met astatic progression. Both nm23 and MVC contribute valuable information in characterizing the malignant phenotype.