Angiogenesis is a multistep process that depends on the balance of proangiogenic factors and inhibitors 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.
To evaluate the relevance of TSP-1 in patients with colorectal cancer.
We examined the immunohistochemical expression of angiogenic agents (VEGF and CD34), proliferation 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.
TSP-1 was detected in the tumor cells, stroma and perivascular tissue. High and moderate tumor TSP-1 expression was observed in 24.75%, weak in 19.6%, while 55.7% of the cases were negative. High stromal expression was observed 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 expression with tumor angiogenesis, growth fraction, p53 protein expression, and overall survival was not significant.
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 extracellular matrix components.
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