The major role of 24-hydroxylase (CYP24A1) is to maintain 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) homeostasis.,Recently, it has been discovered that CYP24A1 also catalyses the hydroxylation of 20(OH)D3, producing dihydroxy-derivatives that show very effective antitumorigenic activities.,Previously we showed a negative correlation of vitamin D receptor (VDR) and CYP27B1 expression with progression, aggressiveness and overall or disease-free survivals of skin melanomas.,Therefore, we analyzed CYP24A1 expression in relation to clinicopathomorphological features of nevi, skin melanomas and metastases.,In melanocytic tumors, the level of CYP24A1 was higher than in the normal epidermis.,The statistically highest mean CYP24A1 level was found in nevi and early stage melanomas.,With melanoma progression, CYP24A1 levels decreased and in advanced stages were comparable to the normal epidermis and metastases.,Furthermore, the CYP24A1 expression positively correlated with VDR and CYP27B1, and negatively correlated with mitotic activity.,Lower CYP24A1 levels correlated with the presence of ulceration, necrosis, nodular type and amelanotic phenotypes.,Moreover, a lack of detectable CYP24A1 expression was related to shorter overall and disease-free survival.,In conclusion, the local vitamin D endocrine system affects melanoma behavior and an elevated level of CYP24A1 appears to have an important impact on the formation of melanocytic nevi and melanomagenesis, or progression, at early stages of tumor development.
Patients with primary cutaneous melanomas that are ulcerated and >2 mm in thickness, >4 mm in thickness and those with nodal micrometastases at diagnosis, have few options for adjuvant treatment.,Recent studies have suggested a role for vitamin D to delay melanoma recurrence and improve overall prognosis.,This is a pilot placebo-controlled randomised phase II trial to assess the feasibility, safety and toxicity of an oral loading dose of Vitamin D (500,000 IU) followed by an oral dose of 50,000 IU of Vitamin D monthly for 2 years in patients who have been treated for cutaneous melanoma by wide excision of the primary.,Patients aged 18 - 79 years who have completed primary surgical treatment and have Stage IIb, IIc, IIIa (N1a, N2a) or IIIb (N1a, N2a) disease are eligible for randomisation 2:1 to active treatment or placebo.,The primary endpoints are sufficiency of dose, adherence to study medication and safety of the drug.,The secondary endpoints are participation and progression free survival.,The study has been approved by the Ethics Review Committee (RPAH Zone) of the Sydney Local Health District, protocol number X09-0138.,Effective, non-toxic adjuvant therapy for high risk primary melanoma is not currently available.,Favorable outcomes of this phase II study will form the basis for a multi-centre phase III study to assess whether the addition of oral high-dose vitamin D therapy in patients who have completed primary treatment for melanoma and are at high risk of recurrence will:prolong time to recurrence within 5 yearsimprove overall survival at 5 years andbe both safe and tolerable.,prolong time to recurrence within 5 years,improve overall survival at 5 years and,be both safe and tolerable.,62 patients have been randomised since the study commenced in December 2010.,Target accrual for the study has been met with 75 patients randomised between December 2010 and August 2014.,The Mel-D trial is conducted by the Australia and New Zealand Melanoma Trials Group (ANZMTG 02.09),Australia and New Zealand Clinical Trials Registry (ANZCTR) ACTRN12609000351213