P53 EXPRESSION ABOVE THE BASAL-CELL LAYER IN ORAL-MUCOSA IS AN EARLY EVENT OF MALIGNANT TRANSFORMATION AND HAS PREDICTIVE VALUE FOR DEVELOPING ORAL SQUAMOUS-CELL CARCINOMA

Epithelial dysplasia is usually used to establish the prognosis of ora l premalignant lesions. Its assessment, however, is subjective and doe s not always correctly predict the outcome of the lesions in terms of malignant transformation. Early molecular alteration(s) that dictate t he development of cancer should be identified and used to evaluate ora l premalignant lesions. In this context, alterations in the expression of p53 were investigated. Thirty-five oral premalignant lesions and 1 1 carcinomas that developed from them in a period of 16 years were inv estigated for p53 expression by immunohistochemistry. Normal oral muco sa front healthy individuals and oral benign lesions were used as cont rols. In benign lesions and normal mucosa, p53 staining, when present, was confined to the basal cell layer, Seven out of 35 (20 per cent) p remalignant lesions showed p53 expression clearly above the basal cell layer and six of these (86 per cent) developed carcinomas. Suprabasal p53 expression was found in three lesions with no or mild dysplasia t hat developed carcinomas. All carcinomas derived from premalignant les ions with p53 suprabasal expression showed p53 expression in neoplasti c cells. The combined use of histological parameters (presence of mode rate or severe dysplasia) with p53 expression patterns (p53 staining a bove the basal cell layer) showed the highest sensitivity for the dete ction of lesions that progressed to carcinoma (91 per cent). When used individually, the p53 expression pattern showed higher specificity th an assessment of dysplasia (96 per cent vs. 54 per cent) and higher po sitive predictive value (86 per cent vs. 44 per cent) for correct pred iction of the malignant transformation of the lesions. The results sug gest that clear expression of p53 above the basal cell laver is an ear ly event in oral carcinogenesis and an indicator of a developing carci noma, even preceding morphological tissue alterations. However, since immunohistochemistry cannot always detect changes in p53 expression in lesions preceding carcinoma, p53 immunohistochemical analysis is stro ngly recommended in conjunction with histological parameters, to incre ase the sensitivity of detection of cases that will progress to carcin oma. (C) 1998 John Wiley & Sons, Ltd.