Expression of p53 in the evolution of squamous cell carcinoma: Correlation with the histology of the lesion

Background: The evolution of squamous cell carcinoma (SCC) on sun-exposed areas is a multistep process triggered by ultraviolet radiation (UVR), in which precursor lesions exist. However, the exact classification of the various lesions in this process, mainly solar keratosis (SK), is still disputed, and its pathogenesis requires further clarification. Objective. To further elucidate the evolution of SCC on sun-damaged skin by correlating the levels of p53 protein expression, a parameter that reflects UVR damage to cells, and the morphology of the lesions that develop on sun-exposed areas. Methods: Biopsy specimens from normal skin (n = 4), normal skin with various degrees of solar elastosis (SE) (n = 16), various degrees of SK (n = 17) and SCCs from sun-exposed (n = 12) and sun-protected (n = 7) areas were stained with anti-p53 antibodies. A semiquantitative evaluation of the degree of staining was performed and correlated with the histological features. Results: Nuclear staining in keratinocytes was observed already in normal skin with mild SE and was increased gradually to its highest level of expression in advanced SK. it was also expressed in SCCs, but to a lesser degree. Statistical analysis revealed association between the morphology of the lesion and the level of p53 expression (P <.01); it also showed that in general the level of p53 is correlated with the histology of the lesion (P <.001). Furthermore, with regard to p53 expression, two groups of lesions exist: one showing a low level of expression of p53 that includes normal skin, skin with various degrees of SE and SCC from sun-protected areas, and a second group showing a high level of expression that includes SK and SCC occurring on sun-damaged skin. Limitation: This is an immunohistochemical study of relatively few cases and in which the antibody detects all types of p53 protein. Conclusions. This study furnishes further evidence that the development of SCC on sun-damaged skin is a gradual process not only morphologically but also on the molecular level. The process starts already in normal-appearing epidermis with SE. In that respect, SK should be regarded as a part of the continuum in the development of SCC, analogous to the situation in other epithelia. The molecular events involved in the development of SCC on sun-exposed areas may be different from those involving the development of SCC on sun-protected areas.