Molecular Mechanisms, Expression and Clinical Role of ErbB Receptors in Endometrial Cancer

The epidermal growth factor system (EGF System) is present in various human organs. It has 4 receptors (EGFR, ErbB-2, ErbB-3 and ErbB-4) and numerous ligands. Especially in cancer, the epidermal growth factor system signaling network becomes hyperactivated with a variety of mechanisms (ligand overproduction, receptor overproduction, constitutive receptor activation). ErbB receptors are trans-membrane glycoproteins. Dimerization of ErbB receptors leads to intracellular kinase activation and initiates intracellular signaling via several pathways. Due to the inactive status of postmenopausal endometrium, we expect to find significantly higher expression of the 4 ErbB receptors in endometrial cancer tissue. In unselected endometrial cancer patients, there is EGFR expression in 43-67% of cases. EGFR overexpression in patients with Type I endometrial cancer, did not affect disease progression. However EGFR overexpression in patients with Type II endometrial cancer, associated with high grade disease and adverse clinical outcome. In unselected endometrial cancer patients, ErbB-2 amplification/overexpression represents a rare event. ΕrbB-2 overexpression especially in patients with Type II endometrial cancer, is an indicator of a highly aggressive disease with poor overall survival. Recent years ErbB receptors (especially EGFR and ΕrbB-2) have a particular importance, as they are potential targets in endometrial cancer treatment