LB947 Progression of chronic sun-damaged skin to actinic keratosis is associated with loss of E-cadherin in keratinocytes

Actinic keratosis are commonly occurring premalignant lesions that are triggered by excessive UV exposure. Their high prevalence and propensity to develop into non-melanoma skin cancer makes them a costly healthcare burden. AKs have the potential to progress to cutaneous squamous cell cancer or to regress back to normal skin. In this study, we examined the natural history of extensive actinic damage in high risk patients (n=26) and evaluated the molecular factors that are associated with progression or regression. AKs were mapped on separate transparent templates at baseline and at months 3, 6, 9 and 11. Skin biopsies were taken at the beginning and end of the study from non-sun exposed (NSE), sun exposed (SE), and a predetermined actinic keratosis (AK). We found that the total number of AKs remained relatively stable over the 11 month observational period. 75.7% of AKs that were present at baseline regressed, of which 32.6% recurred. Immunostaining was conducted on specimens for p53, a key protein in the cellular apoptotic and repair process, and E-cadherin, a marker of epithelial-mesenchymal transitions (EMT), in 10 non-sun exposed, 43 sun exposed, 35 clinically present AKs and 4 regressed AK samples. We also examined expression of E-cadherin transcription repressors, Snail, Slug and Twist, in our skin samples. Clinically apparent AKs expressed significantly less membrane E-cadherin than sun-exposed skin (1.89±1.81, AKs vs. 3.07±1.75, sun-exposed skin; p < 0.005). Moreover, less p53 was observed in regressed AKs than in clinically present AKs (0.75±0.96, regressed AKs vs. 2.89±1.45, clinically apparent AK; p < 0.01). Our results indicate that the loss of E-cadherin expression is closely linked with the persistence of AKs, while loss of p53 is associated with regression. Hence, the dynamic interplay between the regression and recurrence of AKs is associated with notable changes in key biomarkers at the molecular level.