Nuclear expression of the c-erbB-4/HER-4 growth factor receptor in invasive breast cancers

The prevalence and sites of expression of the c-erbB-4 receptor have been determined by immunocytochemical staining in a series of 178 human breast cancers. Most tumors displayed cytoplasmic staining of variable intensity. When compared with adjacent normal tissue, 32 cases (18%) showed lower than normal expression, and 13 (7%) showed greater than normal expression. Nuclear immunoreactivity, confirmed by two different antibodies, was present in 87 cancers (49%) but was found in normal adjacent breast epithelial cells in <5% of cases. There were no significant associations with cytoplasmic or membrane immunoreactivity, but cases showing nuclear expression in >25% of cells were associated with good histological grade, epidermal growth factor receptor expression, c-erbB-3 positivity, cripto, amphiregulin, and transforming growth factor-alpha overexpression.