Actinic keratoses (AKs) are common dysplastic lesions resulting from chronic excessive ultraviolet exposure.,Neither the clinical grade of thickness nor the histological grade of dysplasia seems valid predictors of aggressive potential of AKs.,Instead, the mutational status in AKs appears to predict well the clinical course.,TP53 gene mutations result in a non-functional protein resistant to degradation, thus immunohistochemical staining for p53 can suggest mutation status.,Increased p53 was associated with progression from AK to squamous cell carcinoma.,To investigate how the intensity of p53 staining (p53 staining index) varies according to body site, histological subtype and grade dysplasia of AKs.,Secondly, we sought to investigate the distribution in the epidermal layers of non-functional p53 (zonal staining patterns). p53 staining index was greater than 50% in 90.7% of AKs. p53 staining index was significantly higher in older age (p < 0.0093) and in facial AKs compared to other body areas (p = 0.03).,A significant correlation between p53 staining index and grade of dysplasia was observed (p = 0.006) and between p53 staining index and zonal p53 staining pattern (p = 0.003).,No significant differences in p53 staining index among the various histological AK types were observed.,No correlation between clinical and histological grade.,All AKs, independently from their clinical appearance, should be treated but special attention is required for AKs on severely photodamaged skin on the face and in older patients.
Epidermal squamous cell carcinoma (SCC) is a common and highly invasive form of cancer.,SCC arises due to ultraviolet light exposure and is associated with increased expression of pro-cancer genes and reduced expression of cancer suppressors.,Actin-Like Protein 6A (ACTL6A, BAF53a) is an important protein subunit of the SWI/SNF epigenetic chromatin regulatory complex.,ACTL6A is elevated in cancer cells and has been implicated as a driver of cancer cell proliferation and tumor growth.,In the present study, we show that ACTL6A drives SCC cell proliferation, spheroid formation, invasion and migration, and that these activities are markedly reduced by ACTL6A knockdown.,We further show that ACTL6A expression is associated with reduced levels of the p21Cip1 cyclin-dependent kinase inhibitor and tumor suppressor protein.,Molecular studies show that ACTL6A interacts with p53 DNA response elements in the p21Cip1 gene promoter to suppress p21Cip1 promoter activity and mRNA and protein level.,Additional studies show that an increase in p21Cip1 expression in ACTL6A knockdown cells is required for suppression of the SCC cell phenotype, suggesting that p21Cip1 is a mediator of ACTL6A action.,We further show that this regulation is p53 independent.,These findings suggest that ACTL6A suppresses p21Cip1 promoter activity to reduce p21Cip1 protein as a mechanism to maintain the aggressive epidermal squamous cell carcinoma phenotype.