Objective: The Epidermal Growth Factor (EGF) system is expressed in healthy premenopausal endometrium. We describe the expression of the four receptors, HER1, HER2, HER3, HER4 and the six ligands amphiregulin, transforming growth factor alpha (TGF-alpha), heparin binding EGF like growth factor (HB-EGF), betacellulin, epiregulin and EGF in endometrioid endometrial cancer.
Methods: We have uterine samples from 45 women with endometrioid endometrial cancer. As normal counterparts, endometrial samples from thirteen postmenopausal women, and previous data on fourteen premenopausal women were employed. Extracted RNA was analyzed by real-time PCR; the receptors and ligands were localized by immunohistochemistry.
Results: Three receptors (HER1, HER2 and HER4) and two detectable ligands (TGF-alpha and HB-EGF) are expressed significantly higher in endometrial cancer than in healthy postmenopausal endometrium. Cancer tissue show significantly lower expression of HER1 and HER3, and higher expression of HER4, amphiregulin, TGF-alpha and HB-EGF compared to premenopausal endometrium; no difference is seen in HER2. EGF is undetectable in all of the samples. Immunohistochemically the receptors locate to the epithelium and/or glands while the ligands locate to the stroma (amphiregulin), the stroma and the epithelium (TGF-alpha, epiregulin), the epithelium (betacellulin) or are not detectable (HB-EGF, EGF).
Conclusions: mRNA of all receptors and five ligands are present in endometrioid endometrial cancer, and the protein of all receptors and four ligands are identified by immunohistochemistry. The expression pattern in endometrioid endometrial cancer differs from the pattern in pre- and postmenopausal endometrium. The most remarkable finding is an increased level of HER4, a receptor which correlates to a favorable prognosis in other types of cancers.