Department of Tumor Pathology and Pathomorphology, Oncology Centre-Prof. Franciszek Łukaszczyk Memorial Hospital, The Ludwik Rydygier Collegium Medicum, Nicolaus Copernicus University, 85-796 Bydgoszcz, Poland.
Hum Pathol. 2013 Mar;44(3):374-87. doi: 10.1016/j.humpath.2012.03.031. Epub 2012 Sep 17.
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.
1α-羟化酶（CYP27B1）是合成生物活性维生素 D（1,25(OH)(2)D(3)）的酶，在皮肤中表达。为了评估黑素瘤进展与 CYP27B1 之间的相关性，我们分析了 29 个良性痣、75 个原发性皮肤黑素瘤、40 个转移灶以及 4 个再次切除和 6 个正常皮肤活检组织中 CYP27B1 的表达。与痣和放射性生长阶段肿瘤（分别为 1.2 和 1.1 个任意单位）相比，垂直生长阶段和转移性黑素瘤中的 CYP27B1 免疫反应性显著降低（分别为 0.6 和 0.5 个任意单位）；并且在更晚期的病变中表达减少（Clark 分级 III-V，Breslow 厚度≥2.1mm；分别为 0.8 和 0.7 个任意单位）。CYP27B1 与 Ki-67 表达呈负相关。此外，与非转移黑素瘤相比，导致转移的原发性黑素瘤中 CYP27B1 的表达降低。在放射性生长阶段中，CYP27B1 表达减少与总生存期缩短相关（无、低和高 CYP27B1 免疫反应性黑素瘤的生存时间分别为 810、982 和 1151 天），并且在放射性生长阶段和垂直生长阶段中 CYP27B1 表达减少与无病生存期缩短相关（无、低和高 CYP27B1 免疫反应性黑素瘤的无病生存期分别为 114、339 和 737 天和 129、307 和 737 天）。此外，CYP27B1 在体内黑素瘤细胞和体外培养的黑素瘤细胞中的表达与黑色素呈负相关。因此，CYP27B1 的减少与黑素瘤表型和行为相关，其缺乏会影响黑素瘤患者的生存，表明其在这种癌症的发病机制和进展中发挥作用。
