Microvascular growth of 7,12-dimethylbenz(alpha)anthracene-induced adenocarcinomas in rats: histology and scanning electron microscopy of resin casts

Abstract

Vascular changes at various stages of growth of 7,12-dimethylbenz(alpha)anthracene (DMBA)-induced mammary adenocarcinomas in 22 female Sprague-Dawley rats were investigated using histology, immunohistochemistry and scanning electron microscopy (SEM) of corrosion casts. In the early stage of tumour growth, capillaries within the neoplasms were thin, with 8-10 microm diameter, and characterized by rows of vascular sprouts representing extensive neovascularization and formation of a high-density capillary plexus. In the intermediate stage of tumour growth, the growing tumour was multi-nodular and tumour cells were arranged in a tubulopapillary pattern. Capillaries formed spheroid vascular capsules and were characterized by dilation, to a diameter of 10-80 mum, and blind ends. In the late stage of tumour growth, a remarkable reduction in the number of vascular endothelial growth factor-positive cells and Ki-67-stained nuclei was demonstrated. The tunica media of nutritive arteries displayed a tendency to atrophy. Many arteriovenous anastomoses between the major arteries and the veins were found in regions just before their entry into the tumour. The central regions of the tumour were degenerative and necrotic, and vasculature was confined to surface regions of the tumour, forming a basket-like configuration around the avascular central regions. Resin leakages representing haemorrhage or oedema and distortions such as flattening, break-off and strangulations of capillaries were frequently observed, all of which are known as late tumour signs. We concluded that these microvascular alterations might change the homogeneity of tumour perfusion and contribute to necrosis in central portions of the tumour.