Expression of thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, in several types of malignant tumors has been associated with angiogenesis and an unfavorable prognosis. We performed a retrospective study on the immunohistochemical expression of TP in patients with uterine endometrial cancer to investigate correlations between the expression of TP and the clinicopathologic features and the prognosis. The immunohistochemical staining for TP, CD68 (macrophage/monocyte-specific antibody), and von Willebrand factor was performed in surgically resected specimens from 101 patients with operable endometrial cancer. A semiquantitative grading system was used to examine the staining pattern for TP. Positive staining for both cancer cell and tumor stromal cell TP was noted in 41% of the cases. Most of tumor stromal cells expressing TP were shown to coexpress CD68. High angiogenesis was also associated with TP overexpression in either cancer cells or tumor stromal cells. When stromal macrophages/fibroblasts exhibited high TP expression, independent of whether cancer cells showed the positive TP expression, a significant decrease in disease-free survival and overall survival was observed, which was found to be an independent prognostic factor. Stromal macrophage/fibroblast TP expression remained significant on multivariate analysis. We conclude that (1) TP is present in both cancer cells and stromal macrophages/fibroblasts, (2) high angiogenesis correlated with TP overexpression, (3) TP produced by neighboring tumor-infiltrating macrophages may play a part in the regulation of the local invasion and distant metastatic behavior, and (4) TP overexpression in stromal macrophages/fibroblasts may be associated with a poor prognosis.
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