Abstract
PURPOSE: Angiogenesis is needed to sustain growth of both primary and metastatic lesions; however, comparisons in microvessel density between a primary tumor and its metastases have not been widely performed. We studied microvessel density in primary colorectal cancers and their liver metastases. METHODS: Sections from 32 primary lesions and 53 hepatic metastases were immunostained with a monoclonal antibody for von Willebrand's factor, an endothelial cell marker. Blood vessels were quantified under X 100 magnification using both conventional light microscopy and computer-assisted image analysis. Primary and metastatic angiogenesis 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 analyses were performed using blood vessel to tumor surface area ratios, vessel wall thickness, and intensity of immunostaining. RESULTS: Angiogenesis scores were significantly lower in metastatic lesions compared with their primary tumors (P< 0.0001). Primary AS did not correlate with metastatic tumor size, resectability, multicentricity, or patient survival. Metastatic AS strongly predicted patient survival (P <0.0009) but with a negative coefficient,i.e.,higher scores were associated with improved survival. Metastatic AS were higher in resectable than in nonresectable metastases and in solitary than in multiple metastases; however, these trends were not statistically significant. Metachronous liver lesions had significantly higher angiogenesis scores than synchronous metastases (P <0.04). Similar trends were seen using computer-assisted image analysis. CONCLUSIONS: These results indicate that in presence of an established metastasis, there is a weak angiogenic relationship between a primary tumor and its metastasis. Heterogeneity in metastatic lesions cannot be explained solely by studying angiogenesis 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 metastatic tumor whenever possible may be an indicator of prognosis.
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Funded by the Bowman Research Fund.
Read at the meeting of The American Society of Colon and Rectal Surgeons, Montreal, Quebec, Canada, May 7 to 12, 1995.
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Mooteri, S., Rubin, D., Leurgans, S. et al. Tumor angiogenesis in primary and metastatic colorectal cancers. Dis Colon Rectum 39, 1073–1080 (1996). https://doi.org/10.1007/BF02081403
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DOI: https://doi.org/10.1007/BF02081403