c-erbB-2 oncoprotein detected by automated quantitative immunocytochemistry in breast carcinomas correlates with patients' overall and disease-free survival

Abstract

The prognostic significance of c-erbB-2 oncoprotein overexpression detected in tumours by immunocytochemical assays (ICAs) was investigated in 148 breast carcinomas. ICAs were performed under optimal technical conditions with frozen tissue sections and included automated immunoperoxidase technique and computer-assisted analysis (densitometry) of digitized coloured microscopic images. Results of quantitative ICAs (expressed in percentages of c-erbB-2-positive surfaces and mean optical densities) were correlated with the patients' follow-up in axillary lymph node-positive (N+) and node-negative (N-) subgroups of patients. Patients' follow-up ranged from 9 months (for the first death) to 101 months (for the 121 alive patients) with a 62.5 months mean overall follow-up. It was shown that marked c-erbB-2 immunocytochemical expression in tumours (cut-off point 35%) significantly correlated with the patients' poor overall survival in N+ and in N- patients (Kaplan-Meier, log-rank test, P = 0.045 and P = 0.015). Also, marked c-erbB-2 immunohistochemical expression correlates with short disease-free (P = 0.005), recurrence-free (P = 0.048) and metastasis-free survival (P = 0.05) (Kaplan-Meier, log-rank test) in N+, but not in N- subgroups. It is concluded that in optimal conditions (automated and quantitative ICAs on frozen sections) c-erbB immunohistochemical expression is a significant prognostic indicator in terms of overall and disease-free survival. The c-erbB-2 protein prognostic significance is independent of node status in terms of overall survival, but not of disease-free survival.