erbB-2 oncoprotein expression in breast carcinoma. Poor prognosis associated with high degree of cytoplasmic...

The relationship between immunohistochemically measured membranous expression of erbB-2 oncoprotein and prognosis in breast cancer is controversial, and the relationship between cytoplasmic positivity and prognosis has been minimally investigated. The clinical course of 300 women with infiltrating breast carcinoma, whose tumors were stained for erbB-2 oncoprotein with CB-11 monoclonal antibody, was followed for 5 to 79 months (median, 41 months). Higher numbers of cancer-related deaths were observed in patients with moderate-to-strong cytoplasmic positivity (15/60, 25%) and strong membranous positivity (9/29, 31%) than in patients with negatively stained tumors (8/53, 15%) or tumors with weaker degrees of cytoplasmic or membranous positivity (rate similar to or less than negative tumors). Relapse-free survival was also significantly shorter in patients with tumors with strong membranous positivity and moderate-to-strong cytoplasmic positivity; much of the latter relationship was due to a high number of patients who had erbB-2-positive tumors and who were never disease free. A significant association between decreased relapse-free survival and moderate-to-strong cytoplasmic (but not membranous) positivity persisted even after correction for other variables associated with poor outcome (histologic grade, tumor size, lymph node involvement, and hormone receptor status). Moderate-to-strong erbB-2 oncoprotein cytoplasmic positivity, measured with CB-11 antibody, is associated with a poor prognosis and seems to have biologic significance.