Predictive Role of Thymidine Phosphorylase Expression in Patients with Colorectal Cancer and its Association with Angiogenesis-related Proteins and Extracellular Matrix Components.

摘要

Thymidine phosphorylase (TYMP) is an angiogenic factor that has potent chemotactic activity for endothelial cells and is involved in 5-fluorouracil (5-FU) metabolism. In colorectal cancer (CRC), previous studies evaluating the relationship between TYMP expression and clinicopathological features have yielded inconsistent results. The aim of this study was to investigate the prognostic value of TYMP, its association with other angiogenic factors, proliferation markers and, to our knowledge, for the first time its relationship with extracellular matrix components.Formalin-fixed, paraffin-embedded specimens from 97 patients with CRC were immunostained for TYMP, vascular endothelial growth factor (VEGF), microvascular density (CD34), proliferation marker (Ki-67), proliferating cell nuclear antigen (PCNA), p53 oncoprotein and extracellular matrix components (collagen type IV, fibronectin, tenascin and laminin). Survival curves were calculated with the Kaplan-Meier method.Immunoreactivity was observed in the cytoplasm (cyt) and nucleus (n) of the tumor cells, as well in the stroma (st), endothelium and tumor-associated macrophages. High TYMPcyt expression was observed in 7.2% of the cases, moderate in 22.7% and weak in 59.9%, while 10.3% were negative. High TYMPst expression was observed in 58.8% of the cases. TYMPcyt expression was correlated with the VEGF expression of tumor cells and VEGF expression of vessels (p=0.014 and p=0.022, respectively). TYMPst expression was correlated with VEGF expression and tenascin (p=0.014 and p=0.011, respectively). Patients with higher TYMPcyt expression had a more favorable overall survival (p=0.041) in univariate analysis compared to patients without TYMP expression.These findings suggest that TYMP plays an important role in angiogenesis, extracellular matrix remodeling and in the prognosis of patients with CRC, but further studies are needed to clearly define its role in CRC.