Background  Photodynamic therapy (PDT) has been shown to be effective in treating nonmelanoma skin cancer (NMSC), especially actinic keratosis (AK). Moreover, there is sufficient evidence of its effectiveness in preventing the appearance of premalignant and malignant lesions in organ transplant recipients.

Objectives  To describe the molecular and genetic changes underlying this preventive effect.

Methods  Twenty-two patients with AK were treated with methyl aminolaevulinate and red light. Biopsies were performed before and 6 weeks after the treatment. Conventional histopathology and immunohistochemistry were carried out.

Results  Not only was a reduction in the dysplasia and elastosis observed, but also a decreased expression of Ki-67 and p53. The abnormal findings did not disappear completely in all cases. The expression of cyclin D1 remained stable.

Conclusions  These findings show that PDT has the potential to reduce the histological signs of photoageing. Moreover, the reduction of Ki-67, a marker of proliferation and of p53, a marker of early skin carcinogenesis, indicates a reversal of the carcinogenic process. On the other hand, the fact that one treatment does not clear dysplasia and expression of p53 completely, and the persistence of cyclin D1, indicate that one single treatment, despite showing good clinical results, is not sufficient to clear completely the signs of chronic actinic damage, and thus the risk of NMSC.