title: High density of small vessels expressing the tyrosine kinase receptor KDR in primary invasive breast carcinoma correlates with axillary lymph node metastases.
abstract: Although it is generally accepted that tumour growth is angiogenesis dependent, little is known about the role of angiogenesis in the metastatic process. Recent evidence suggests that the angiogenic tyrosine kinase receptor KDR is pivotal in new vessel formation. To investigate, therefore, the association between new vessel formation in primary breast carcinoma and axillary lymph node metastasis we have used computer assisted video analysis to assess the vascular distribution as well as the level of expression of KDR in individual vessels in sections of invasive breast carcinomas, some of which had metastasized to the axillary lymph nodes and some that had not. We specifically assessed the frequency distribution, perimeter, area, and density of KDR positive vessels in the same sections of tumours. Our results show that in invasive mammary carcinoma KDR is expressed exclusively on the surface and cytoplasm of endothelial cells of approximately 71% of vessels, but the level of expression in individual vessels does not correlate with the presence of axillary lymph node metastases (P > 0.10). However, we found that small vessels express higher levels of KDR (P < 0.02) than larger vessels and that there is a significantly higher frequency of relatively small (< 90 microm in perimeter) KDR positive vessels in breast tumours that had metastasized to the axillary lymph nodes than those that had not (P < 0.001). In conclusion, increased density and frequency of KDR positive small vessels in primary invasive breast carcinoma correlates with axillary lymph node metastases.