The Type 1 family of growth factor receptors includes epidermal growth fact
or receptor (EGFR), c-erbB-2, c-erbB-3 and c-erbB-4. Overexpression of the
first two members is associated with poorer prognosis in patients with brea
st carcinoma. In this study we examined the expression of c-erbB-4 protein
using the monoclonal antibody HFR-1. A total of 127 consecutive cases of pr
imary operable invasive breast carcinoma presenting between 1975 and 1977 w
ere studied. All patients were managed by simple mastectomy or conservation
surgery with radiotherapy and no adjuvant therapy given. Long-term follow-
up was maintained. Routine, formalin-fixed, paraffin-embedded tumour sample
s were used and sections were stained immunohistochemically using the Duet
StreptABC method. Immunoreactivity was classified using a simple semi-quant
itative scoring method. Protein expression was generally low but definite p
ositive cytoplasmic, membranous and nuclear reactivity was identified in 58
%, 41% and 25% of cases respectively. Expression at all three sites demonst
rated significant inverse associations were histological grade. In addition
, membrane accentuation correlated inversely with the Nottingham Prognostic
Index (NPI), while cytoplasmic reactivity showed a positive association wi
th c-erbB-3 expression. No significant associations were found with disease
-free interval or survival. The results of this study demonstrate that high
er levels of c-erbB-4 protein expression are associated with a more differe
ntiated histological phenotype in contrast to the other members of the Type
1 family. Larger series with extended follow-up will be required to ascert
ain definitively the prognostic value of c-erbB-4 expression in breast carc
inoma. (C) 2000 Cancer Research Campaign.