1α-Hydroxylase (
CYP27B1), the
enzyme responsible for the synthesis of the biologically active form of
vitamin D (
1,25(OH)(2)D(3)), is expressed in the skin. To assess the correlation between progression of melanocytic
tumors and
CYP27B1, we analyzed its expression in 29 benign
nevi, 75 primary cutaneous
melanomas, 40
metastases, and 4 re-excision and 6 normal skin biopsies. Immunoreactivity for
CYP27B1 was significantly lower in the vertical growth phase and metastatic
melanomas (0.6 and 0.5 arbitrary units, respectively) in comparison with
nevi and radial growth phase
tumors (1.2 and 1.1 arbitrary units, respectively); and expression was reduced in more advanced lesions (Clark levels III-V, Breslow thickness ≥2.1 mm; 0.8 and 0.7 arbitrary units, respectively). There was an inverse correlation between
CYP27B1 and Ki-67 expression. Furthermore,
CYP27B1 expression was reduced in primary
melanomas that created
metastases in comparison with non-metastasizing
melanomas. Reduced
CYP27B1 expression in radial growth phase was related to shorter overall survival (810 versus 982 versus 1151 days in
melanomas with absent, low, and high
CYP27B1 immunoreactivity), and low
CYP27B1 expression in radial growth phase and vertical growth phase was related to shorter disease-free survival (114 versus 339 versus 737 days and 129 versus 307 versus 737 days, respectively, in
melanomas with absent, low, and high
CYP27B1). Also,
CYP27B1 expression was inversely related to
melanin in
melanoma cells in vivo and
melanoma cells cultured in vitro. Thus, reduction of
CYP27B1 correlates with
melanoma phenotype and behavior, and its lack affects the survival of
melanoma patients, indicating a role in the pathogenesis and progression of this
cancer.