Apollon Karseladze
N. Blokhin Cancer Research Center,Russian Federation
Title: Impairment of vascularization of the surface covering epithelium induces ischemia and promotes malignization: a new hypothesis of a possible mechanism of cancer pathogenesis
Biography
Biography: Apollon Karseladze
Abstract
Purpose: To study the peculiarities of vascularization at the stromal-epithelial interface in different types of epithelia and their alterations in precancerous lesions. Material & Methods: Peritumoral tissues of 310 patients, tissues of 180 healthy persons and of 50 human embryos and foetuses have been taken. Traditional histological as well as immunohistochemical methods have been used. Results: The study reveals that the occurrence of blood capillaries in surface squamous epithelium is an ordinary event, both in healthy persons and in peritumoral regions of the patients with squamous cell carcinoma. As soon as precancerous dysplastic alterations start and progress the number of intraepithelial blood vessels simultaneously decreases, thus leading to ischemia which precedes or promotes malignization of the covering squamous epithelium. To compensate for the deficit in blood supply, the dysplastic cells penetrate deeper into the underlying stroma, commencing invasion. Thus, the cells destroy the subjacent stroma not because they are initially “malignant”, but due to ischemia which provokes the search for nutrients. Glandular epithelial coverings, (e.g. respiratory epithelium) do not contain blood vessels, since each cell is attached directly to the basal membrane and has more ample access to the blood supply. In squamous epithelium, only basal cells are in contact with the membrane and underlying stroma, the cells of the upper layer receiving nutrients through diffusion. Thus the cells of squamous epithelium are more vulnerable to blood deficiency. Metaplastic squamous epithelium has a markedly reduced vascularization and seems to be more sensitive to carcinogenic stimuli. High-grade dysplastic squamous epithelium and carcinoma in situ do not contain blood vessels at all. Furthermore, the specific composition of basal membrane for each type of epithelium may regulate the ingrowth of blood capillaries into surface linings. Conclusion: The process of redistribution of vascular network occurring at the interface of epithelial- stromal frontier plays an important role in maintaining the adequate metabolism of cells including those of epithelial covering. Impairment of this mechanism most probably promotes precancerous alterations (dysplasia).