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PMID: 26910282 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Melanin content in melanoma metastases affects the outcome of radiotherapy.

Oncotarget ·Vol. 7 ·No. 14 ·2016-04-05 ·Pages 17844-53

Brożyna AA, Jóźwicki W, Roszkowski K, Filipiak J, Slominski AT

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.

Keywords
melanin melanoma radiotherapy survival
MeSH Terms
Adult Aged Aged, 80 and over Cohort Studies Female Humans Male Melanins/metabolism Melanoma/metabolism,radiotherapy Middle Aged Neoplasm Metastasis Skin Neoplasms/metabolism,radiotherapy
Chemicals
Melanins
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Brożyna Anna A
Department of Tumour Pathology and Pathomorphology, Oncology Centre-Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland. | Department of Tumour Pathology and Pathomorphology, Faculty of Health Sciences, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.
Jóźwicki Wojciech
Department of Tumour Pathology and Pathomorphology, Oncology Centre-Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland. | Department of Tumour Pathology and Pathomorphology, Faculty of Health Sciences, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.
Roszkowski Krzysztof
Department of Oncology, Radiotherapy and Gynecologic Oncology, Faculty of Health Sciences, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz, Bydgoszcz, Poland.
Filipiak Jan
Department of Chemotherapy, Oncology Centre-Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland.
Slominski Andrzej T
Departments of Dermatology and Pathology, University of Alabama at Birmingham, Birmingham, AL, USA. | Laboratory Service of The VA Medical Center at Birmingham, Birmingham, AL, USA.
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Article Info
Journal
Oncotarget
Abbr.
Oncotarget
ISSN
1949-2553
DOI
10.18632/oncotarget.7528
Published
2016-04-05
Pages
17844-53
Language
English
Region
United States
NLM ID
101532965
PMCID
PMC4951254
Subset
IM
Grants
NIAMS NIH HHS · R01 AR056666 · United States
NIAMS NIH HHS · 1R01AR056666-01A2 · United States
External Links
PubMed source DOI: 10.18632/oncotarget.7528 PMC Full Text View journal details
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