// Anna A. Brożyna 1, 2 , Wojciech J&oacute;źwicki 1, 2 , Krzysztof Roszkowski 3 , Jan Filipiak 4 , Andrzej T. Slominski 5, 6 1 Department of Tumour Pathology and Pathomorphology, Oncology Centre-Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland 2 Department of Tumour Pathology and Pathomorphology, Faculty of Health Sciences, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland 3 Department of Oncology, Radiotherapy and Gynecologic Oncology, Faculty of Health Sciences, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland 4 Department of Chemotherapy, Oncology Centre-Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland 5 Departments of Dermatology and Pathology, University of Alabama at Birmingham, Birmingham, AL, USA 6 Laboratory Service of the VA Medical Center at Birmingham, Birmingham, AL, USA Correspondence to: Anna A. Brożyna, e-mail: anna.brozyna@cm.umk.pl Andrzej Slominski, e-mail: aslominski@uabmc.edu Keywords: melanoma, melanin, survival, radiotherapy Received: January 14, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Accepted: February 11, 2016&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Published: February 20, 2016 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.

Melanin content in melanoma metastases affects the outcome of radiotherapy