Association Between Thrombospondin-1, Angiogenesis Related Markers, and Extracellular Matrix Components with Colorectal Cancer Outcome

Abstract

Background: Angiogenesis is a multistep process that depends on the balance of proangiogenic factors and in- hibitors as well as on interactions with the extracellular matrix. Thrombospondin-1 (TSP-1) is an endogenous inhibitor of angiogenesis encoded by THBS1 gene, whose promoter is activated by p53. Aim: To evaluate the relevance of TSP-1 in patients with colorectal cancer. Material and Methods: We examined the immunohistochemical expression of angiogenic agents (VEGF and CD34), pro- liferation associated indices, extracellular matrix components (tenascin, fibronectin, laminin, and collagen type IV), and the antiangiogenic agent TPS-1 in 97 patients with colorectal carcinoma (CRC) and correlated their expression levels with clinicopathological parameters. Results: TSP-1 was detected in the tumor cells, stroma and perivascular tissue. High and moderate tumor TSP-1 expres- sion was observed in 24.75%, weak in 19.6%, while 55.7% of the cases were negative. High stromal expression was ob- served in 40.2% and perivascular stain was noted in 31.95% of the cases. Stromal TSP-1 expression was correlated with tumor type and tumor grade (p=0.001, and p=0.041 respectively) and with ECM components expression: tenascin (p=0.053), fibronectin (p=0.063), collagen type IV (p=0.004) and laminin (p=0.0001). The relationship of TSP-1 expres- sion with tumor angiogenesis, growth fraction, p53 protein expression, and overall survival was not significant. Conclusions: Our data suggest that both tumor and stromal TSP-1 expression may not be a direct antiangiogenic factor, although it seems to be implicated in the remodeling of colorectal cancer tissue through interaction with other extracellu- lar matrix components.