Abstract 2909: LC3 protein expression associates with UV exposure in melanoma histopathology

Abstract The 5-year survival rate for stage IV melanoma is estimated to remain unchanged at only 15%, even with new therapies. One emerging hallmark of cancer is the reprogramming of energy metabolism including the role of autophagy. In cancer, autophagy appears to be an important energy source for nutrient-depleted tumors. Ultraviolet-radiation (UVR) exposure is an established risk factor for melanoma and increases autophagic flux. We hypothesize that UV exposure is independently associated with both levels of autophagy and melanoma survival. To address this hypothesis, we are investigating the association between UVR exposure, autophagy, and development of melanoma. Basal levels of autophagy appear to vary by tumor stage, and higher levels of autophagy are associated with poor clinical prognosis. Melanoma cells contain high levels of autophagosomes, a cellular structure associated with autophagy, as measured by the proxy marker LC3. Also, the expression of the autophagy marker Beclin 1 has been associated with increased risk of early death from melanoma. These findings suggest that autophagy provides metabolic support for tumors as it localizes to hypoxic tumor areas, supports tumor cell survival, and is activated in response to stress. Autophagy can act as a cytoprotective mechanism against UV-induced apoptosis. We have shown that rates of autophagy vary by oncogene status. Autophagy was evaluated in formalin-fixed, paraffin embedded melanoma and normal tissue sections, by staining for LC3 and Beclin 1 using IHC. These markers of autophagy, along with clinical tumor characteristics, were correlated with extensive questionnaire data on UV exposure from the same patients to evaluate the impact of estimated lifetime sun exposure and sunburns on survival. A trend in the expression of Beclin1 was not observed; however, LC3 expression was increased in melanoma sections compared to normal. Our results provide enticing support that lifetime UVR exposure is associated with autophagy protein expression in melanoma. Citation Format: Kirsten A. M. White, Salina Torres, Todd A. Thompson, Chien-An A. Hu, Orrin Myers, Marianne Berwick. LC3 protein expression associates with UV exposure in melanoma histopathology. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2909. doi:10.1158/1538-7445.AM2015-2909