Type 1 protein tyrosine kinases in benign and malignant breast lesions

Aims: To determine their significance, we examined the expression pattern o f the four epidermal growth factor receptor (EGFR) family members as well a s the phosphotyrosine kinase activity in breast tumour tissues. Methods and results: Fifty-three malignant breast tumours, four breast canc er cell lines, and 10 benign breast tumours were investigated. Fifty-three per cent (28/53) of the malignant tumours expressed EGFR protein, and the m ajority of these positive tumours were strongly positive. Eighty per cent ( 8/10) of the benign tumours also expressed EGFR protein, but all in a lower or moderate level. An association between EGFR expression and increasing m alignancy grade was found in the group of infiltrating ductal carcinomas. O f the malignant tumours, 35.8% (19/53) expressed c-erbB-2 protein and 17% ( 9/53) c-erbB-3 protein, while no expression of c-erbB-2 and c-erbB-3 protei ns was found in the benign rumours, Contrary to previous reports, we observ ed c-erbB-4 receptor protein to be less expressed in the malignant breast t umours. The 'normal' breast epithelial cells adjacent to the malignant tumo urs and the benign tumours demonstrated intensified membrane staining for c -erbB-4, while a number of the malignant tumours demonstrated a weak cytopl asmic staining or were negative. However, several malignant tumours with st rong membrane staining for the c-erbB-4 protein were also found, No simple association between the expression of the four receptors and phosphotyrosin e kinase activity was found. Conclusion: Our study has revealed a complex expression pattern of the EGFR family members in breast tumour cells. While the data about EGFR, c-erbB-2 , c-erbB-3 and phosphotyrosine are largely in line with what has been repor ted, we found the c-erbB-4 protein expression to be decreased in the malign ant tumours.