1. ¹Department of Pathology, Democritus University of Thrace Medical School, Alexandroupolis, Greece
2. ²Department of Radiotherapy/Oncology, Democritus University of Thrace Medical School, Alexandroupolis, Greece
3. ³Department of Pathology, Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Oxford, UK
4. ⁴Cancer Research UK, Molecular Oncology Laboratories, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK

Correspondence: Dr A Giatromanolaki, MD, Department of Pathology, Democritus University of Thrace Medical School, PO Box 12, Alexandroupolis 68100, Greece. E-mail: targ@her.forthnet.gr

Received 21 December 2005; Revised 31 January 2006; Accepted 5 February 2006; Published online 24 March 2006.

Abstract

Vascular endothelial growth factor (VEGF) is a potent angiogenic factor for many malignant neoplasms exerting its function through activation of specific membrane receptors, that is, KDR/flk-1, residing in endothelial cells. Several recent reports indicate that VEGF receptors are also expressed in cancer cells, suggesting that specific VEGF-originated cancer cell reactions may parallel the endothelial response. Using a novel monoclonal antibody, recognizing the activated (phosphorylated) form of the KDR receptor (pKDR), we assessed the expression of pKDR in normal and malignant endometrium. A strong and consistent cytoplasmic and nuclear pKDR expression was noted in the normally cycling endometrium, including epithelial, stromal and endothelial cells, suggesting a role in the normal menstrual cycle. Approximately, one-third of the 70 stage I endometrioid adenocarcinomas analysed exhibited an intense cytoplasmic and nuclear pKDR expression in both cancer cells and peritumoral vessels. It was noted that such pKDR reactivity in cancer cells was related directly to VEGF, VEGF/KDR complexes and HIF1 (hypoxia inducible factor 1) expression. Furthermore, pKDR expression was significantly associated with poor prognosis. It is concluded that the VEGF/KDR pathway is activated in both normally cycling and malignant endometrium, suggestive of an important role in the biology of this tissue. The unfavourable prognosis that VEGF confers to endometrial adenocarcinomas could be attributed to its angiogenic activity, but also to a direct effect on cancer cells through an autocrine VEGF/KDR loop.