Investigation of environmental factors for diagnosing malignant potential in oral epithelial dysplasia

A study was conducted in rats with early tongue carcinoma induced by 4-nitroquinoline 1-oxide (4NQO), in order to investigate the early diagnosis of malignant potential of epithelial dysplasia. The rat tongue lesions were classified by their severity into three groups corresponding to early cancer, dysplasia and no change. The grade of epithelial changes was determined according to 13 items of WHO Epithelial Dysplasia Criteria. The expression levels of p53 and Bcl-2 proteins were detected immunohistochemically, and apoptotic cells were detected using the TUNEL method. In addition, a p53 mutation by lesions was detected. The expression ratio of p53 protein was high in dysplasia, and the ratio of Bcl-2 protein was high in early cancer and dysplasia. The TUNEL-positive cells were observed primarily in the granular layers of the no change cells, and their numbers decreased as the cells shifted to the early cancer stage. The p53 mutation was detected using a microdissection method in dysplasia, where it was found in three out of nine lesions. All the mutations in dysplasia detected were on the same codon that was found to be mutated in the early cancer. These results indicate that the association between the p53 mutation and histological changes in carcinogenesis epithelial dysplasia is strong, and that both the identification of p53- and Bcl-2-positive epithelium, and decrease in the TUNEL positive ratio, were useful for the diagnosis of the malignant potential of precancerous lesions.