Staton CA et al. (2007) The angiogenic switch occurs at the adenoma stage of the adenoma–carcinoma sequence in colorectal cancer. Gut 56: 1426–1432

In addition to its role as a key initiator of blood coagulation, tissue factor (TF) also upregulates vascular endothelial growth factor (VEGF), a highly potent stimulator of angiogenesis. The stage at which angiogenesis begins (the 'angiogenic switch') in the adenoma–carcinoma sequence (ACS) of colorectal cancer progression, however, is not clear. Staton and colleagues therefore examined the expression of TF and VEGF and microvascular density at different stages of colorectal cancer.

Historical surgical specimens from 210 patients were histopathologically examined; these specimens represented a range of colorectal cancer development stages, including background mucosa, low-grade and high-grade dysplastic polyps and Dukes' grade A, B and C carcinoma. Fresh tissue specimens from 90 patients who underwent removal of primary colorectal cancer were also examined.

Microvascular density (measured using the cumulative Chalkley score) increased significantly with progression along the ACS (P <0.0005), and was also positively correlated with the Dukes' stage (P = 0.013) and lymph node involvement (P = 0.023). The largest increase in the cumulative Chalkley score was observed at the onset of dysplasia. Semiquantitative analysis of TF and VEGF expression showed a positive correlation between the levels of these two markers of angiogenesis in the initial phase of the ACS (P <0.005), but not with microvascular invasion, tumor size, Dukes' grade, lymph node involvement or survival.

The authors' findings suggest that the angiogenic switch occurs at the onset of dysplastic transformation of colorectal polyps, and that the correlation between TF and VEGF levels might highlight the importance of these markers in angiogenesis and disease progression.