Reciprocal expression of epidermal growth factor receptor (EGF-R) and c-erbB2 by non-invasive and invasive human trophoblast populations.

Trophoblast invasion of the maternal uterus during human placentation is a highly complex process involving proliferation, migration and cell differentiation. Tyrosine kinase receptors are known to be involved in such functions. The epidermal growth factor-receptor (EGF-R) and c-erbB2 proto-oncogene products are two closely related tyrosine kinase receptors which are expressed in high amounts in human placenta. In this study, we have investigated the expression of EGF-R and c-erbB2 proteins by different trophoblast populations using immunohistochemistry. EGF-R was expressed by proliferative villous cytotrophoblasts, but not by non-proliferative, invasive, extravillous cytotrophoblasts. In contrast, c-erbB2 was expressed by invasive extravillous trophoblasts (EVT) but not by villous cytotrophoblasts. Expression of both receptors was seen only by the terminally differentiated placental bed giant cell and villous syncytiotrophoblast populations. This precise spatial expression suggests that EGF-R plays an important role in trophoblast proliferation whereas c-erbB2 may be important for trophoblast invasion and differentiation. The surface expression of these receptors on normal isolated first trimester trophoblasts and on choriocarcinoma cell lines was also investigated by flow cytometry, and compared with that of the c-erbB2-overexpressing mammary tumour cell line BT474. Isolated trophoblasts were shown not to overexpress c-erbB2, and no differences in either EGF-R or c-erbB2 expression were seen between normal and malignant trophoblasts.