Future directions in the field of endometrial cancer research: the need to investigate the tumor microenvironment.

Endometrial cancer is the most commonly diagnosed gynecologic malignancy in the United States. In 2008, approximately 40,000 cases were newly diagnosed. Although the majority of these cancers are curable by means of hysterectomy and radiotherapy, a subset of endometrial tumors exhibits an aggressive phenotype characterized by lymphovascular invasion, high histological grade, and myometrial invasion, leading to poor prognosis. The mechanisms involved in this aggressive transformation are largely unknown, however, interactions between the primary tumor mass and the surrounding stroma likely play a role in this transformation. Despite the fact that research in other common malignancies has elucidated important associations between stromal protein expression and invasion, these mechanisms have been poorly explored in the area of endometrial cancer. In fact, few investigations have been conducted in the area of tumor microenvironment for endometrial tumors. Invasion and metastasis are two primary reasons for treatment failure related to endometrial cancer. Expression of stromal-derived proteins can potentially serve as biomarkers of aggressive disease as well as biomarkers for remission monitoring. In order to study how expression of these proteins relates to the prognosis of endometrial cancer, these proteins need to be explored in large sets of existing data and/or tissue banks. In this paper, we briefly review the role of three stromal related pathways, SDF-1alpha/CXCR4, HGF/c-Met, and VEGF-A in endometrial cancer prognosis as an overview of the literature. We report that the role of SDF-1alpha/CXCR4 and HGF/c-Met in endometrial cancer prognosis remains unclear, whereas the evidence pertaining to VEGF indicates that overexpression is involved in tumor growth and metastasis. Finally, we would like to highlight the need to explore stromal proteins as a potential tool for the detection of aggressive endometrial tumors and explore some of the molecular approaches that can be utilized in the exploration of the tumor environment.