Influence of VEGFR and LHCGR on endometrial adenocarcinoma

Abstract

Endometrial adenocarcinoma is a common gynecological malignancy that is usually treated by surgical resection followed by radiation. However, the frequency of remote metastasis is high. The present study aimed to investigate whether patients with endometrial adenocar- cinoma exhibited a positive response to treatment with a gonadotropin-releasing hormone analogue or inhibitors of neoangiogenesis, which are applied for the treatment of other malignancies. Immunohistochemical analyses were performed using 203 paraffin-embedded tissue samples of endometrial adenocarcinomas from patients who had undergone surgery at the Department of Obstetrics and Gynecology of the Ludwig Maximilians University of Munich, Germany. The tissues were incubated with antibodies against luteinizing hormone/choriogonadotropin receptor (LHCGR) and vascular endothelial growth factor receptor 2 (VEGFR2), and evaluated by bright field microscopy. The staining was categorized according to the Immune-Reactive-Score (IRS). The IRS scores were then statistically associated with various tumor traits, including tumor size, lymph node status, metastasis, grade, expression of steroid hormone receptors and patient survival. There was a significant association between VEGFR2 expression and tumor grading and estrogen receptor-α (ERα). For LHCGR, a correlation was observed with ERα and progesterone receptor (PR). No correlations were identified between VEGFR2 or LHCGR expression and the other examined tumor traits or patient survival. The associations between VEGFR2 and ERα, and between LHCGR and ERα or PR, may be explained by the interaction of these signal transduction molecules in the regulation of cellular growth and differentiation. These mechanisms also have an important role in the formation of remote metastases, which is the main cause for tumor-associated mortality. The results of the present study suggested that patients with endometrial adenocarcinoma may benefit from treatment with inhibitors of ERα, PR, VEGFR2 or LHCGR, since it could lead to a better prognosis. However, further studies are required in order to elucidate the roles of these receptors in endometrial adenocarcinoma.