Alterations in the volume of the intercellular space between epithelial cells of the hamster cheek-pouch: quantitative studies of normal and carcinogen-treated tissues.

Abstract

The present report investigated the extent of the epithelial dysplastic feature known as "loss of cellular adherence" at the ultrastructural level by quantifying the volume of the intercellular space during hamster cheek-pouch carcinogenesis. Following topical application of DMBA to cheek-pouches, lesions were classified as hyperplasia, dysplasia and carcinoma, with untreated pouches serving as a control. Stereological point counting procedures were used to determine the volume density of intercellular space in defined basal, spinous and granular layers for each group. In general, progressive increases in volume density were detected within each stratum during carcinogenesis. These results indicate that increasing separation of epithelial cells occurs during carcinogenesis, although it is not yet known whether this results from loss of cohesion between specialised (i.e., desmosomal) or nonspecialised membrane areas. In addition, a simple indicator of pathological alteration, the Pathological Alteration Ratio (PAR), is described and was used to evaluate existing published data for intercellular spaces in various oral mucosal conditions. Values of the PAR were found to be substantially higher in carcinogen-treated epithelia than in reports describing changes in wound healing, lichen planus and leukoplakia simplex. These objective techniques are of value for investigating the pathogenesis of diseased epithelium and may find applications in the diagnosis of oral premalignant lesions.