TUMOR ANGIOGENESIS IN PRIMARY AND METASTATIC COLORECTAL CANCERS

PURPOSE: Angiogenesis is needed to sustain growth of both primary and metastatic lesions; however, comparisons in microvessel density betwee n a primary tumor and its metastases have not been widely performed. W e studied microvessel density in primary colorectal cancers and their liver metastases. METHODS: Sections from 32 primary lesions and 53 hep atic metastases were immunostained with a monoclonal antibody for von Willebrand's factor, an endothelial cell marker. Blood vessels were qu antified under X100 magnification using both conventional light micros copy and computer-assisted image analysis. Primary and metastatic angi ogenesis scores (AS), i.e., vessel counts, were analyzed with respect to tumor size, hepatic multicentricity, synchronicity, resectability, and patient survival. Using computer-assisted calculations, the same a nalyses were performed using blood vessel to tumor surface area ratios , vessel wall thickness, and intensity of immunostaining. RESULTS: Ang iogenesis scores were significantly lower in metastatic lesions compar ed with their primary tumors (P < 0.0001). Primary AS did not correlat e with metastatic tumor size, resectability, multicentricity, or patie nt survival. Metastatic AS strongly predicted patient survival (P < 0. 0009) but with a negative coefficient, i.e., higher scores were associ ated with improved survival. Metastatic AS were higher in resectable t han in nonresectable metastases and in solitary than in multiple metas tases; however, these trends were not statistically significant. Metac hronous liver lesions had significantly higher angiogenesis scores tha n synchronous metastases (P < 0.04). Similar trends were seen using co mputer-assisted image analysis. CONCLUSIONS: These results indicate th at in presence of an established metastasis, there is a weak angiogeni c relationship between a primary tumor and its metastasis. Heterogenei ty in metastatic lesions cannot be explained solely by studying angiog enesis in primary tumors. Microvessel, density in a primary tumor may not be useful as an independent prognostic indicator in late stages of disease. In such cases, assessment of microvessel density in a metast atic tumor whenever possible may be an indicator of prognosis.