Immunohistochemical Expression of c-erbB2, c-erbB3 and c-erbB4 Protein in Breast Cancer

Breast cancer is the third leading cause of cancer related deaths in Korean women. Members of the erhB receptor family, the EGF receptor and c-erbB2, c-erbB3 and c-erbB4. are commonly over-expressed in human breast cancer and there is a high correlation with an aggressive breast cancer phenotype and poor patient prognosis. Since the over~expression of the EGF receptor and c-erbB2 suggested that signalling of erbB receptors may contribute to the development and progression of breast cancer, we investigated the correlation of clinicopathological factors and the immunohistochemical expression of c-erbB2, c-erhB3 and c-erbB4. To detennine the c-erhB immunoreactivity, we used Rabbit anti-human c-erbB2 oncoprotein (DAKO, Denmark), mouse monoclonal c-erbB3(RTJ.2, Santa Cruz) and rabbit polyclonal antibody c-erbB4(Santa Cruz) directed against each c-erbB protein by immunohistochemistry from paraffin-embedded tissue in a series of 190 women with breast cancer. About 25.8%(49 out of 190 patients) of breast cancers overexpressed c-erbB2, and 40.0%(76 out of 190 patients) and 18.9%(36 out of 190 palieuts) overexpressed c-erbB3 and c-erbB4, respectively. Poor histologic grade showed tendency of positive correlation of the positivity of c-erbB2 and 3 but without statistical significance and no correlation with c-erbB4. We observed positive correlations among c-erbB2, c-erhB3 and c-erbB4 expression.(p<0.05) Estrogen receptors (ER) showed inverse correlations with c-erbB2(p=-0.OOl), c-erbB3(p=0.043) and c-erbB4(p-0.197) and progesterone receptors also showed inverse correlation with c-erbB2(p-O.018). Tumor size (p>O.05) and lymph node status(p>O.05) were not related with c-erbB family expression. The expressions of c-erbB2, c-erbB3 and c-erbB4 showed no survival benefit or no disease free benefit compared to c-erhB family negativity in univariate analysis (Kaplan-Meier life table analysis). Our results suggest that c-erbB2, c-erbB3 and c-erbB4 may regulate the growth of breast cancer by the interactions of these family of growth factor receptor that are dependent of honnonal control. (Korean J of Breast Cancer 1998;1:215225)