NM23 - RELATIONSHIP TO THE METASTATIC POTENTIAL OF BREAST-CARCINOMA CELL-LINES, PRIMARY HUMAN XENOGRAFTS, AND LYMPH-NODE NEGATIVE BREAST-CARCINOMA PATIENTS

BACKGROUND. Since the discovery of nm23 (nonmetastatic) by Steeg et al . in 1988, a number of tumor cohort studies have shown, an inverse rel ationship between the levels of expression of the nm23-H1 protein and disease aggressiveness and tumor metastatic potential. METHODS. The re lationship between the expression of nm23 protein and the metastatic p otential of human breast carcinoma was analyzed in cell lines, xenogra fts, and in a retrospective lymph nude negative breast carcinoma popul ation. The lymph node negative breast carcinoma study was comprised of 40 patients: 19 with nonrecurrent and 21 with recurrent disease. The 40 patients were matched according to age, cathepsin D, tumor size, pe rcent S-phase, DNA ploidy, steroid receptor status, and tumor grade. N m23-H1 protein levels in cell lines and xenografts were analyzed quant itatively using Western blot analyses and semiquantitatively in tissue sections using immunocytochemistry. Immunocytochemical analysis of ly mph node negative breast tumors was graded as the percent of tumor sta ining positive for nm23 and the intensity of staining. The metastatic potentials of the cell lines and xenografts were assessed as the abili ty to form metastatic lesions in nude mice. In the lymph node negative breast carcinoma patients, the metastatic potential was characterized as the incidence of breast carcinoma recurrence. RESULTS. The MCF-7 c ell line expressed four- and tenfold higher levels of nm23-H1 than the highly metastatic MDA-MB-435 and MDA-MB-231 cells, respectively. Amon g the xenografts and cell lines, there was an inverse correlation betw een Nm23-H1 expression and metastatic potential in athymic nude mice ( correlation coefficient [R] = -0.51). The differences between the leve ls of nm23-H1 among the metastatic and nonmetastatic cell lines and xe nografts were not statistically significant. Statistical analyses indi cated that neither the intensity nor the percent of tumor staining pos itive for nm23 expression was correlated to the recurrence of breast c arcinoma in the lymph node negative patient population that had been m atched for other clinical prognostic markers. CONCLUSIONS. There was a n inverse correlation (R = -0.51) between the levels of nm23-H1 expres sion in cell lines and xenografts and the metastatic potential in nude mice. In the retrospective lymph node negative breast carcinoma popul ation, no clear association was demonstrated between the expression of nm23 and breast carcinoma recurrence. This observation suggests the n m23 expression does not predict outcome in lymph node negative breast carcinoma patients. (C) 1997 American Cancer Society.