Reduced expression of nm23‐H1, but not of nm23‐H2, is concordant with the frequency of lymph‐node metastasis of human breast cancer

Abstract

The nm23 gene is a potential metastasis‐suppressor gene originally identified in a murine melanoma line. Several investigators have reported the probable inverse association of nm23 expression with disease prognosis and/or metastasis. Since there are now 2 known isotypes of human nm23, namely nm23‐H1 and ‐H2, we immunohistochemically examined expression of these isotypes in human breast‐cancer tissues using monoclonal antibodies (MAbs) specific for each isotype protein. We also analyzed expression of c‐erbB‐2 in the same collection of cancer tissues, in order to examine the significance of nm23 expression in comparison with c‐erbB‐2 expression. Of 130 tumors from breast‐cancer patients, 73 (56%) and 69 (53%) positively expressed nm23‐H1 and ‐H2 respectively. Expression of c‐erbB‐2 was positive in 36 (28%). Expression of nm23‐H1, but not nm23‐H2, was inversely associated with lymph‐node metastasis (p < 0.01). Expression of c‐erbB‐2 was associated with Tnm stage, tumor size and lymph‐node metastasis (p < 0.01, p < 0.05 and p < 0.05 respectively). Overall survival was better (p = 0.014) in patients in whom expression of nm23‐H1 was positive than in those in whom it was negative. In multivariate analyses using a Cox's proportional‐hazards regression model with 9 variables, nm23‐H1 showed the fourth greatest contribution to patient survival following lymph‐node metastasis, Tnm stage and menopausal status. No significant contribution was shown for c‐erbB‐2 expression. nm23‐H1, but not nm23‐H2, may perform a role in disease prognosis in addition to its participation in cancer metastasis. It may have value for predicting long‐term survival of human breast‐cancer patients.