La terapia fotodinámica y sus implicaciones en la prevención de queratosis actínicas y carcinoma epidermoide

Resumo

Photodynamic therapy (PDT) has been shown to be effective to treat nonmelanoma skin cancer (NMSC), especially, actinic keratosis (AK). Moreover there is sufficient evidence of its effectiveness to prevent the appearance of premalignant and malignant lesions in organ transplant recipients. The aim of this study is to describe the molecular and genetic changes underlying this preventive effect. Therefore 22 patients were treated with using methylaminolevulinate and red light. Biopsies were performed before and six weeks after the treatment. Conventional histopathology and immunohistochemistry were carried out. In addition western blot and RNA-microarrays were performed using proteins and RNA extracted from the skin samples. Not only was a reduction in the dysplasia and elastosis observed, but also a decreased expression of ki-67 and p53. These abnormal findings did not disappear completely in all cases. The expression of cyclin D1 remained stable and COX-2 showed a slight tendency to overexpressión. No statistically significant differences were found in the gene expression profiling. These findings show that PDT has the potential to reduce the histological signs of photoaging. Moreover, the reduction of ki-67, marker of proliferation, p53, marker of early skin carcinogenesis, indicate a reversion of the carcinogenic process. The meaning of the tendency to overexpression of COX-2 should be studied more deeply. The fact that no changes were found in the arrays might be due to the high genetical variability of the human being and the low number of cases studied. On the other hand the fact that one treatment does not clear dysplasia and expression of p53 completely, and the persistence of cycllin 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.