Abstract
Melanin possess radioprotective and scavenging properties, and its presence can affect the behavior of melanoma cells, its surrounding environment and susceptibility to the therapy, as showed in vitro experiments. To determine whether melanin presence in melanoma affects the efficiency of radiotherapy (RTH) we evaluated the survival time after RTH treatment in metastatic melanoma patients (n = 57). In another cohort of melanoma patients (n = 84), the relationship between melanin level and pT and pN status was determined. A significantly longer survival time was found in patients with amelanotic metastatic melanomas in comparison to the melanotic ones, who were treated with either RTH or chemotherapy (CHTH) and RTH. These differences were more significant in a group of melanoma patients treated only with RTH. A detailed analysis of primary melanomas revealed that melanin levels were significantly higher in melanoma cells invading reticular dermis than the papillary dermis. A significant reduction of melanin pigmentation in pT3 and pT4 melanomas in comparison to pT1 and T2 tumors was observed. However, melanin levels measured in pT3-pT4 melanomas developing metastases (pN1-3, pM1) were higher than in pN0 and pM0 cases. The presence of melanin in metastatic melanoma cells decreases the outcome of radiotherapy, and melanin synthesis is related to higher disease advancement. Based on our previous cell-based and clinical research and present research we also suggest that inhibition of melanogenesis can improve radiotherapy modalities. The mechanism of relationship between melanogenesis and efficacy of RTH requires additional studies, including larger melanoma patients population and orthotopic, imageable mouse models of metastatic melanoma.
Highlights
Cutaneous melanoma is the most rapidly increasing malignancy in the Caucasian population, and the transition from the radial growth phase (RGP) to the vertical growth phase (VGP) has an important negative impact on patient survival [1,2,3,4]
Analysis of cohort A showed a significantly longer survival time of patients with amelanotic metastatic melanomas in comparison to the melanotic ones, who were treated with either RTH and CHTH or RTH (Figure 1A–1D, Table 1). These differences were more evident in the group of melanoma patients treated only with RTH (Figure 1B) in comparison to patients treated with both radio- and chemotherapy (Figure 1A) (Table 1)
Following our previous studies on reverse relationship between melanoma melanization levels and OS and disease-free survival (DFS) in patients at stages III and IV disease [35], we analyzed the outcome of RTH in relation to pigmentation level of melanoma metastatic cells
Summary
Cutaneous melanoma is the most rapidly increasing malignancy in the Caucasian population, and the transition from the radial growth phase (RGP) to the vertical growth phase (VGP) has an important negative impact on patient survival [1,2,3,4]. Melanomas at this stage have metastatic capability, and once the metastatic process has started, the survival rate of patients decreases dramatically [3,4,5,6]. Recent published data has shown, that induction of melanogenesis is related to significant up-regulation of HIF-1α and HIF-1-dependent pathways, contributing to the increased aggressiveness of melanoma [34]. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz Poland during the period of 2006–2012
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