23 Tumour angiogenesis in primary colorectal carcinoma

Abstract

Angiogenesis is considered a key event in tumour growth and metastasis. Detailed information on tumour angiogenesis and its regulation, might predict clinical outcome and the sensitivity of radiotherapy. It might also lead to more efficient drug delivery and facilitate the development of angioinhibitors. We have investigated the microvascular supply in human primary and metastatic colorectal adenocarcinomas. Although overall vascular density between tumour tissue and surrounding colorectal mucosa differed only moderately, we could identify the presence of a collagen IV positive membrane as a demarcation for more intense angiogenic response in the stroma. We could also identify vascular hot spots, similar to the concept developed in other solid tumours, e.g. breast cancer. The MVD (microvessel density) was calculated in the “hot spots” and expressed as the number of vessels/X250 field. The MVD of different hot spots within the same tumour section showed a very low variability whereas the intertumour variability was markedly higher. In an attempt to correlate areas of most intense vascularity with proliferation in tumour cells and endothelial cells, we developed a double staining technique with CD3l and Ki-67. These studies showed an impressive percentage of cycling endothelial cells within the tumour compared with the normal colon mucosa and the adjacent mucosa (21% vs 0.59% vs 1.5%). Within tumours the regional differences in MVD correlate with differences in turnour cell proliferation. The presence or absence of p53 expression was also found to be correlated to the MVD.