PROGNOSTIC-SIGNIFICANCE OF NM23 NDPK EXPRESSION IN BREAST-CARCINOMA, ASSESSED ON 10-YEAR FOLLOW-UP BY AUTOMATED AND QUANTITATIVE IMMUNOCYTOCHEMICAL ASSAYS/

The Nm23 gene has been described as an antimetastatic gene; in some st udies, disease progression in patients with solid tumours is related t o Nm23 protein expression, which can be detected by immunohistochemica l procedures. Detection of Nm23-H-1 protein in breast cancer may be re levant for the monitoring of patient therapy, provided that the techni cal procedures are reliable and cost-effective. The aim of the present study was to determine the prognostic significance of Nm23, assessed by quantitative immunocytochemical assays (Nm23 ICAs), under optimal t echnical conditions. Nm23-H-1 ICAs were performed on frozen sections, using an automated immunoperoxidase technique (Ventana) and computer-a ssisted analysis of digitized colour microscopic images (SAMBA), in a series of 168 breast carcinomas. The results of automated quantitative ICAs were correlated with patients' follow-up (129 months), Nm23-H-1 immunocytochemical expression in histological sections of tumours in w hich more than 3 per cent of the surface area was positively stained w as significantly (0.012) correlated with longer metastasis-free surviv al in both node-positive and node-negative groups of patients (P=0.032 and P=0.036, respectively) (Kaplan-Meier log-rank test, NCSS 6.0.1 so ftware), Nm23 expression (cut-point 3 per cent) did not, however, corr elate with overall survival, or with the recurrence-free survival. In multivariate analysis (proportional hazards regression, Cox model), th e prognostic significance of Nm23 in terms of metastasis-free survival was independent of tumour size and grade, and of histological grade, in the entire cohort of patients. It is concluded that Nm23 immunodete ction is only of limited practical clinical relevance in breast carcin oma, even when assessed under optimal technical conditions. (C) 1998 J ohn Wiley & Sons, Ltd.