3D microvascular architecture of pre-cancerous lesions and invasive carcinomas of the colon

Despite the significance of tumour neoangiogenesis and the extensive knowle dge on the molecular basis of blood vessel formation currently no quantitat ive data exist on the 3D microvascular architecture in human primary tumour s and their precursor lesions. This prompted us to examine the 3D vascular network of normal colon mucosa, adenomas and invasive carcinomas by means o f quantitative microvascular corrosion casting. Fresh hemicolectomy specime ns from 20 patients undergoing cancer or polyposis coli surgery were used f or corrosion casting, factor VIII and VEGF immunostaining. In addition, imm unostaining was done on colorectal tissue from 33 patients with metastatic and non-metastatic carcinomas? polyposis coli and adenomas. This first quan titative analysis of intervessel and interbranching distances, branching an gles and vessel diameters in human cancer specimens revealed distinct patte rns of the microvascular unit in the tumour centre and periphery. Irrespect ive of the tumour localization and grading all individual tumours displayed qualitatively and quantitatively the same vascular architecture. This give s further evidence for the existence of a tumour type-specific vascular arc hitecture as recently demonstrated for experimental tumours. Metastatic tum ours displayed different vascular architectures only within hot spots, in t erms of smaller intervascular distances than in non-metastatic tumours. Pre -cancerous lesions have in part virtually the same vascular architecture li ke invasive carcinomas. Comparison of VEGF immunostaining also suggests tha t angiogenesis sets in long before the progress towards invasive phenotypes and that the so-called angiogenic switch is more likely a sequence of even ts. (C) 2001 Cancer Research Campaign.