Predictive role of thymidine phosphorylase expression in patients with colorectal cancer and its association with angiogenesis-related proteins and extracellular matrix components.

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Association of syndecan-1 with angiogenesis-related markers, extracellular matrix components, and clinicopathological features in colorectal carcinoma.

Syndecan-1 is a transmembrane heparansulfate proteoglycan, which regulates cell proliferation, migration, angiogenesis, cell-to-cell and cell-to-extracellular matrix adhesion and may influence malignant cell behavior. We investigated the alterations of syndecan-1 expression in colorectal cancer and analyzed the relationship between clinicopathological parameters, proliferation indices, angiogenic markers, and extracellular matrix components. Syndecan-1 protein expression observed in the tumorous epithelium was high in 52/97 (53.6%) of the studied cases, moderate in 20/97 (20.6%), and weak in 5/97 (5.22%) of the cases, and there was strong stromal expression in 34.02% of the tumors. Syndecan-1 expression was statistically correlated to VEGF expression in tumor (p=0.001) and vessels (p=0.007). In addition, there was a borderline correlation between syndecan-1 expression and tenascin (p=0.053). Patients with weak staining reaction had a more unfavorable prognosis (p=0.032) in univariate analysis. These results indicate the implication of syndecan-1 in the remodeling and angiogenesis of colorectal cancer tissue, through interaction with other extracellular matrix components and VEGF, probably influencing the tumor progression and aggressiveness.