Association between melanoma and dermal mast cell prevalence in sun-unexposed skin

Abstract

Background: Both exposure to intermittent intense sunlight during childhood and ultraviolet (UV) radiation-induced immunomodulation have been directly associated with melanoma development. In mice, the prevalence of dermal mast cells determines susceptibility to UVB-induced systemic suppression of contact hypersensitivity responses and thus may affect immunological responses to melanoma antigens. Objectives To determine the relevance of murine studies of dermal mast cell prevalence to human melanoma pathogenesis. Methods: The prevalence of mast cells was examined in sun-unexposed buttock skin of 45 melanoma patients and 68 control volunteers who had no history of skin cancer development. Buttock skin was studied because mast cell prevalence is stable with ageing and the confounding effects of environmental UV exposure are minimized. Results: Using tissue immunostaining, the buttock skin from melanoma patients had a significantly higher dermal mast cell prevalence (mean ± SEM 38 ± 2 mast cells mm−2) than controls (32 ± 2 mast cells mm−2) (P = 0·02). Analysis by binary logistic regression showed that the association between mast cell prevalence and melanoma outcome was not significantly altered by skin phototype. Conclusions: The immunomodulatory effects of mast cell products in UV-irradiated skin may contribute significantly to the initiation and development of human cutaneous malignant melanoma.