Reproducibility and Expression of Skin Biomarkers in Sun-Damaged Skin and Actinic Keratoses

Abstract

To explore p53 and proliferating cell nuclear antigen (PCNA) expression and polyamine content as biomarkers in skin cancer chemoprevention trials, we evaluated their expression in early stages of UV-induced squamous cell tumorigenesis. Biopsies were collected from three groups: 78 subjects with sun damage on forearms, 33 with actinic keratosis (AK) on forearms, and 32 with previous squamous cell carcinoma. Participants with sun damage were randomized to sunscreen or no sunscreen. We found significant differences in p53 and polyamines in forearms from the sun-damaged group (11.5 +/- 1.2% for p53, 65.5 +/- 1.9 nmol/g for putrescine, and 187.7 +/- 3.3 nmol/g for spermidine) compared with the group with sun damage plus AK (20.9 +/- 2.3% for p53, P = 0.0001; 81.7 +/- 3.9 nmol/g for putrescine, P = 0.0001; 209.4 +/- 8.2 nmol/g for spermidine, P < 0.06). PCNA was not different. When lesion histology was considered, there was a stepwise significant increase in p53 in biopsies without characteristics of AK compared with early AK (P = 0.02) and AK (P = 0.0006) and a similar pattern for PCNA with the only significant difference between early AK and AK. There was a stepwise increase in putrescine and spermidine in normal, sun-damaged forearm, forearm from subjects with AK, and the AK lesion itself (P < 0.0001). No significant differences in p53 or polyamines were seen in 3-month biopsies or, as a result of sunscreen use, although PCNA in the sun-damaged group not using sunscreen decreased significantly. p53 expression and polyamines in skin were elevated in early stages of skin tumorigenesis and were not affected by sunscreen, adding validity to their use as biomarkers in skin cancer chemoprevention trials.