EXPRESSION OF METASTASIS-ASSOCIATED GENES H-MTSL (S100A4) AND NM23 INCARCINOMA OF BREAST IS RELATED TO DISEASE PROGRESSION

The murine 18A2/mts1 and its human homolog h-mts1 (S100A4), encoding a Ca2+-binding protein belonging to the S-100 family, are associated wi th high invasive and metastatic potentials of murine tumors, human tum or cell lines in vitro, and human tumors growing as xenografts. The nm 23 is a putative metastasis-suppressor gene whose expression has been found to correlate inversely with the metastatic potential of some for ms of human cancer. The products of both human genes alter cytoskeleta l dynamics, with antagonistic effects. In view of the equivocal associ ation of nm23 with the metastatic potential of human cancer, we suspec ted that the relative expression of h-mts1 and nm23 might reflect tumo r progression more accurately than either of them alone. We describe h ere the expression of these genes in infiltrating ductal carcinomas of the breast and show that high h-mts1 expression is associated with me tastatic spread to the regional lymph nodes. The expression of nm23 on its own did not show a statistically significant inverse correlation with nodal spread. However, the expression status of the two genes, ta ken together, correlated strongly with the occurrence of nodal metasta ses. Breast cancers with no detectable expression of h-mts1 were found to be estrogen and progesterone receptor positive. Expression of h-mt s1 was not related to tumor differentiation. The clinical data, togeth er with the state of expression of steroid receptors and the expressio n levels of h-mts1 and nm23 genes, were analyzed using artificial neur al networks for accuracy in predicting nodal spread of the carcinomas. These analyses support the conclusion that, overall, h-mts1 expressio n appears to be associated with and indicative of more aggressive dise ase. Complemented with nm23, h-mts1 could provide a powerful marker of breast cancer prognosis.