INTRODUCTION
Epidemiology
Actinic keratosis (AK) is a premalignant skin lesion that may result from prolonged ultraviolet (UV) damage.1 AKs are common worldwide with an estimated global prevalence rate of 14%.1 AKs are often characterized as hyperkeratotic papules or plaques with a rough surface or overlying scale on an erythematous base.2–4 These skin lesions often appear on sun-exposed areas and are more common among males, those of advanced age, those with Fitzpatrick skin type I or II, and those who are immunosuppressed.1,4 If left untreated, AKs may progress to invasive squamous cell carcinoma (SCC).2,4
Pathogenesis
Histologically, AKs demonstrate epidermal hyperplasia and varying degrees of cellular atypia.2 The atypia can resemble SCC in situ but without full-thickness epidermal involvement.2 The cellular changes that are present in both AKs and SCCs may be indicative of their mutual pathogenesis.2 AK development commonly begins with DNA damage in the basal layer of the epidermis.2,5 Affected keratinocytes often contain DNA mutations that have been classically associated with UVB-related damage (eg, C to T and CC to TT).2,5 The mutations have also been associated with oxidative stress from UVA-mediated production of reactive oxygen species or the intrinsic aging of cells.2 The DNA mutations found in AKs particularly involve the TP53 gene, which encodes for the p53 protein that plays a critical role in tumor suppression.5 The TP53 mutations contribute to keratinocyte dysplasia, ultimately resulting in AK development on the epidermal surface.2,5 In the research of AK progression to SCC, Src kinases have been of particular interest, as increased expression of these nonreceptor tyrosine kinases has been found in both AKs and SCCs.6,7 Studies suggest that increased Src signaling may play an important role in the alteration of hemidesmosomes and migration of keratinocytes necessary for SCC progression and invasion.6,7
