Tumor angiogenesis in primary and metastatic colorectal cancers

Dis Colon Rectum. 1996 Oct;39(10):1073-80. doi: 10.1007/BF02081403.


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.

MeSH terms

  • Biomarkers, Tumor / analysis
  • Colorectal Neoplasms / pathology*
  • Female
  • Humans
  • Image Processing, Computer-Assisted
  • Liver Neoplasms / pathology*
  • Liver Neoplasms / secondary
  • Male
  • Microcirculation
  • Neoplasms, Multiple Primary / pathology*
  • Neoplasms, Multiple Primary / secondary
  • Neoplasms, Second Primary / pathology*
  • Neoplasms, Second Primary / secondary
  • Neovascularization, Pathologic / pathology*
  • Predictive Value of Tests
  • Prognosis
  • Survival Rate
  • von Willebrand Factor / analysis


  • Biomarkers, Tumor
  • von Willebrand Factor