Overexpression of p53 Protein Associated with Proliferative Activity and Histological Degree of Malignancy in Solar Keratosis

BACKGROUND: Overexpression of p53 protein has frequently been demonstrated in human epithelial neoplasms including squamous cell carcinoma (SCC) and solar keratosis (SK). SK is a precursor lesion of SCC. In SCC of the skin, we have already reported that overexpression of p53 protein is associated with the proliferative activity, which is indicated by the percentage of Ki-67-positive cells. In SK, however, the significance of p53 overexpression is still unclear. OBJECTIVE: The aim of the present study was to clarify the relationship between p53 overexpression and proliferative activity, and between p53 overexpression and histological degree of malignancy in SK. METHODS: Sixty-eight cases of SK were divided into four grades according to the proportion of atypical cells in the epidermis (in grade I, up to 25% of the epidermal cells are atypical, in grade II 25-50%, in grade III 50-75%, in grade IV more than 75%) and were immunohistochemically analyzed for the expression of p53 protein and Ki-67 antigen. RESULTS: p53 overexpression was detected in 58 out of the 68 cases of SK. The percentage of p53-protein-positive cells (DO-7 index) ranged from 0 to 78.8 (mean +/- SD = 20.6 +/- 21.6). Mean DO-7 indices were 7.9 in grade I, 26.7 in grade II and 38.3 in grade III. The differences in mean DO-7 index between grades I and II and between grades I and III were statistically significant (p < 0.001). The percentage of Ki-67-antigen-positive cells (MIB-1 index) ranged from 0.8 to 38.2 (mean +/- SD = 10.5 +/- 9.0). Mean MIB-1 indices were 5.9 in grade I, 10.7 in grade II and 20.5 in grade III. The differences in the mean MIB-1 index between grades I and II and between grades II and III were statistically significant (p < 0.01). Cases with higher DO-7 indices tended to show higher MIB-1 indices, and the relation was statistically significant [y = 0.272x + 4.8; correlation coefficient r = 0.59 > r (n - 2, 0.01) = 0.31]. CONCLUSION: Overexpression of p53 protein was related to cell proliferation as well as histological degree of malignancy in SK. Dysfunction of p53 protein might be implicated in skin carcinogenesis.