072 Targeting field cancerisation in epidermal cancers

Abstract

Ultra-Violet (UV) radiation from sunlight is the main carcinogen driving epidermal cancers of the skin. The accumulation of UV-induced mutations on sun-exposed areas leads to field cancerisation. Knowing the regenerative property of the skin, we investigated if epidermal ablation removes mutations on the epidermis and allows less mutated cells from the deeper part of the skin to repopulate the ablated surface. Patients with history of multiple epidermal cancers were subjected to epidermal ablation on their forearms with three different depths of laser (600nm, 400nm and fractional laser). Deep targeted DNA sequencing of 151 cancer related genes had revealed the mutation burdens on ablated and non-ablated epidermis. There were 12.9 mutations per Megabase (Muts/Mb) found in non-ablated control epidermis compared to 2.55 Muts/Mb in 600nm, 4.45 Muts/Mb in 400nm and 3.58 Muts/Mb in fractional laser ablated and regenerated epidermis (n=7). To evaluate the efficacy of epidermal ablation on epidermal cancers formation, we utilised a UVB inducible Basal Cell Carcinomas (BCC) murine model (K14Cre/ER::Ptch1lox/+ ). These mice were subjected to a total of 20 weeks of UVB radiation. Half of the dorsal epidermis was dermabrased after the first 10 weeks of radiation. Wholemount staining of a BCC biomarker, Keratin-17 (K17), revealed a significant reduction in the number of K17 patches in dermabrased area (0.35 patches/mm2 ± 0.04 compared to 0.07 patches/mm2 ± 0.03) suggesting dermabrsasion can be used to reduce BCC occurrence. Overall, our findings propose a potential technique to reverse the photo-damage process by removing the mutations accumulated on the epidermis. This study may also pave the way to a larger clinical trial of epidermal ablation as an adjuvant therapy for high-risk epidermal cancer patients.