p53 GENE ALTERATIONS AND p53 PROTEIN IN ORAL EPITHELIAL DYSPLASIA AND SQUAMOUS CELL CARCINOMA

Abstract

To examine the expression of p53 protein and gene alterations in oral epithelial lesions including epithelial dysplasias and primary squamous cell carcinomas, immunohistochemical and temperature gradient gel electrophoresis (TGGE) methods were applied to formalin-fixed and paraffin-embedded tissues. Morphologically normal mucosal epithelium stained negatively for p53 protein. Three out of 11 (27.3 per cent) epithelial dysplasias and 19 out of 57 (33.3 per cent) primary squamous cell carcinomas stained positively for p53 protein. Although more than half of the cases were positive for p53 protein in stage I, the positive cancer cases were found at other stages with variable frequency. Immunoreactive products were localized in the nucleus, especially in the basal and suprabasal layers. The analysis by TGGE revealed gene alterations in exons 5-8 in 3 out of 3 epithelial dysplasias and 17 out of 19 (89.5 per cent) primary squamous cell carcinomas which were immunohistochemically positive for p53 protein. These results suggest that p53 gene mutation may be involved in carcinogenesis in the oral squamous epithelium even in the early stage of the dysplasia-carcinoma sequence.

High frequency of p53 mutations in human oral epithelial dysplasia and primary squamous cell carcinoma detected by yeast functional assay

“…In contrast, in 14 displastic lesions, 36% was positive for p53 mutation (Figure 2). Although relatively few studies have been made as to p53 mutations in oral premalignant lesions, 15.4% (Lazarus et al, 1995) or 27% (Kusama et al, 1996) of epithelial dysplasia has been reported to be positive for p53 mutation. Since it has been shown that the malignant potential of leukoplakia is as high as 23 ± 38% (Silverman et al, 1984), mutations of the p53 gene may be indicative of the potential of these lesions to develop into SCC.…”

“…The timing of p53 mutations has been studied best in colorectal adenocarcinoma where mutations of p53 gene most frequently occur between the stages of late adenoma and invasive carcinoma (Fearon and Vogelstein, 1990). Mutations of p53 have also been observed in a variety of non-invasive, dysplastic epithelial lesions from various tissues, including oral cavity (Lazarus et al, 1995;Kusama et al, 1996), esophagus (Casson et al, 1991;Bennett et al, 1992), and lung (Sozzi et al, 1992). These data suggest that mutations of p53 gene may be an early event in squamous epithelium during progression to cancer.…”

A Case of Extensive Erythroplakia in the Oral Mucosa.

“…Alteration of the p53 gene is known to be detectable in 50% of squamous cell carcinomas of the head and neck (21,22). No reaction for p53 protein was observed in this case, suggesting that the possibility of carcinogenesis was low.…”

Activation-induced cytidine deaminase mRNA expression in oral squamous cell carcinoma-derived cell lines is upregulated by inflammatory cytokines

“…It is an invasive epithelial neoplasm of the oral cavity showing various degrees of squamous differentiation, and a propensity for early and extensive lymph node metastasis (17). Kusama et al have previously demonstrated p53 mutation in OSCC, suggesting that this mutation is involved in the early stages of the dysplasia-carcinoma sequence in the oral squamous epithelium (18). Moreover, recent studies have suggested an association between periodontal disease and the risk of various human malignant neoplasms, including poorly differentiated OSCC (19,20).…”