The contribution of neuronal–glial–endothelial–epithelial interactions to colon carcinogenesis
Studies of experimental tumors in rodents indicate that there are morphological abnormalities of the tumor microcirculation compared to normal tissues. The aim of this study was to examine the structure of the microvasculature in benign and malignant colonic tumors in humans using microvascular casting techniques. There were 15 adenocarcinomas, four benign sporadic adenomas, and three specimens from patients with familial adenomatous polyposis (FAP). A cast of the microvessels of these tumors was prepared by intraarterial administration of acrylic resin (Mercox) and the cast examined by scanning electron microscopy. Quantitative measures of the microvasculature were obtained from histological sections using stereological techniques in four carcinomas, two sporadic adenomas, and 12 adenomas from patients with FAP. Vascular casts of benign colonic adenomas showed that the microvasculature had a similar organization to normal colon. However, capillaries and venules were elongated and had increased diameters compared to normal. In adenomas greater than 3 mm in diameter, there was an increased density of microvessels in the spaces between tumor cells. Vascular casts of colonic carcinomas were characterized by a disorganized structure and increased density of microvessels. The organization of microvessels within carcinomas had a similar overall pattern to normal colon. However, the increased number and density of microvessels resulted in formation of nodular clusters of capillaries, formation of “sheets” of frequently anastomosing capillaries, or almost complete packing of the interstitial spaces of the tumor by capillaries in places. Most capillaries had a long and tortuous course and numerous capillary sprouts were identified. Tumor microvessels had greater mean diameters than normal. Extravasation of resin from microvessels in carcinomas was frequently seen. The vascular volume of carcinomas (23.1%±12.2), sporadic adenomas (16.3%±3.4), and adenomas >3 mm diameter in patients with FAP (17.7%±3.0) were significantly greater than in normal colon (11.0%±4.2). This study indicates that there is an increased vascular density in benign and malignant tumors of the colon compared to normal colon. The presence of profusely anastomotic microvessels and frequent capillary sprouts is evidence of active neovascularization and suggests control of tumor growth could be achieved by modifiers of angiogenesis.