Effect of topical tretinoin, chemical peeling and dermabrasion on p53 expression in facial skin.

The tumour suppressor protein p53 is a phosphoprotein that is activated by DNA damage. It is involved in the decision whether the cells should stop replication and proceed to repair their DNA, or to die by apoptosis. In the present study, we evaluate the effect of some treatment modalities on the expression of p53 in facial skin. Biopsy specimens were obtained from the facial skin of 20 patients before and after treatment using topical tretinoin (11 cases), TCA chemical peeling (5 cases) and dermabrasion (4 cases). Biopsy specimens were also obtained from 12 control subjects representing the same age groups of the patients. Topical tretinoin therapy was found to induce a significant decrease in the expression of p53 up to 6 months of therapy followed by a significant increase after 10 months of therapy. On the contrary, superficial TCA peeling did not induce any statistically significant change in the expression of p53. On the other hand dermabrasion was found to induce a significant decrease in the level of expression of p53 in biopsies obtained after complete re-epithelialization followed by a significant increase. These changes in the expression of p53 may play a role in mediating the effects of such treatment modalities on the epidermis, as well as prevention of actinic neoplasia by adjusting any disturbance in the proliferation/apoptosis balance observed in photoaged facial skin.

Expression of p53 in normal sun-exposed and protected skin (type IV-V) in different decades of age.

The checkpoint protein p53, which is activated by DNA damage, is involved in the decision whether the cells should stop replication and proceed to repair their DNA or die by apoptosis. We evaluate the expression of p53 and the number of apoptotic cells in normal sun-exposed (face) and protected (abdomen) skin in Egyptians between 6 and 77 years of age. The degree of p53 expression in facial skin significantly increases from a score of 1.5 +/- 1.5 (mean +/- SEM) in the 1st decade to 4.8 +/- 0.3 in the 8th decade (p = 0.02), while no significant changes are detected in the protected skin (p = 0.1). Overall, the level of expression is significantly higher in sun-exposed facial skin than in abdominal skin (p = 0.007). However, p53 expression versus age is significantly higher in the facial skin of older age groups in both males (p = 0.003) and females (p = 0.02). The pattern of staining was found to be dispersed (wild-type) in the majority (97.3%) of biopsies from sun-exposed skin and in all biopsies from non-exposed skin. The expression of wild-type p53 in type IV-V skin therefore correlates with both site and age of the individual. In contrast, the number of apoptotic cells significantly decreases with advancing age in sun-exposed skin (p = 0.005). Increased age-associated expression of p53 in sun-exposed skin, but not in protected areas of skin, is found to reflect an accumulation of the wild-type protein, as judged by the staining pattern. The decrease in apoptotic cells with age may suggest the accumulation of senescent cells in the skin and their relative resistance to apoptosis. Such alteration in the proliferation/apoptosis balance could play a role in tumorigenesis.