PURPOSE: Angiogenesis, as measured by degree of microvessel density, has been associated with tumor progression in many tumor types but does not always correlate with clinical outcome. In 1999, aggressive tumor cells were shown to form blood-conducting tubes not lined by endothelial cells, and this phenomenon was termed vasculogenic mimicry. We investigated angiogenesis and the presence of vasculogenic mimicry in colorectal carcinoma in relation to tumor stage, patient survival, and genetic indicators of tumor cell plasticity. METHODS: Paraffin-embedded tissue samples were examined from a study of 117 patients with colorectal carcinoma with a 12-year follow-up. Immunohistochemical analysis was used to measure microvessel density and proliferating endothelial cells and to detect vasculogenic mimicry (scored by 3 independent observers). Cell cultures from 7 colon cell lines, real-time polymerase chain reaction (PCR) on cell lines, frozen tissue material from 4 colorectal cancer patients with and 4 without vasculogenic mimicry, and fresh colorectal cancer tissue from 2 patients were used to investigate the relationship between vasculogenic mimicry and tumor cell plasticity. RESULTS: Microvessel density was not a prognostic marker in our patients. We found vasculogenic mimicry in 23 (19.7%) of 117 colorectal tumor samples. Cell culture experiments and real-time PCR on human colorectal carcinoma material showed evidence for vasculogenic mimicry with overexpression of EPHA2 and LAMC2, known to be important for the tube-forming capacity of melanoma tumor cells. The presence of vasculogenic mimicry was associated with significantly shortened survival, both overall (P < 0.0001) and within intermediate cancer stages (Dukes B, P = 0.0277; Dukes C, P < 0.0001). CONCLUSIONS: Vasculogenic mimicry can occur in colorectal carcinoma and appears to be comparable to vasculogenic mimicry described in other tumors. Moreover, vasculogenic mimicry in colorectal carcinoma may be a strong independent prognostic marker for survival.