Abstract
Recent studies involving melanoma cell lines suggest that enhanced expression of epigenetic regulator RNF2 supports proliferation and promotes metastasis. However, it is not clear to what extent those data apply to disease progression and prognosis for melanoma patients. Therefore the aim of the present study was to assess the prognostic power of RNF2 intratumoral expression by melanoma cells.RNF2 was detected immunohistochemically in standard formalin-fixed paraffin-embedded samples of 9 benign nevi, 60 melanomas and 24 nodal metastases.The lowest percentage of RNF2-positive melanocytes found in nevi was comparable to expression levels in normal skin. The RNF2 expression found in melanomas was significantly higher and it was even more enhanced in metastases. The increased occurrence of RNF2 expressing cells was positively correlated with longer patients’ overall survival. Moreover, a negative correlation was found between intratumoral RNF2 expression and number of generated metastatic lesions.Our data indicate that development of melanoma is associated with significant changes in RNF2 intratumoral expression and imply that at least for some patients the enhancement of the expression levels of RNF2 in both primary and metastatic lesions may be considered a favorable prognostic factor in melanoma.
Highlights
Melanoma causes 90% of skin cancer deaths [1]
We show in this work that expression of RNF2 by melanocytes of benign nevi and of a normal skin is similar
Similar observation for normal human skin was reported by Sánchez-Beato et www.oncotarget.com www.oncotarget.com al. [13] who carried out immunohistochemical studies of RNF2 expression in tissue microarrays
Summary
Melanoma causes 90% of skin cancer deaths [1]. Mean survival time of patients with distant melanoma metastases is of the order of 1 year. For that group of the patients the probability of 1 year survival is 45% and the 5 year survival rate is 10% [2]. Despite recent progress in developing new therapies the melanoma survival rates have not changed significantly. Epigenetic regulation has emerged as an important area in the field of cancer biology with a special focus on a role of epigenetic regulators in controlling mechanisms of cancerogenesis, cancer diagnostics and prognostication. Because of the potential reversibility the epigenetic changes studies of the epigenetic factors may lead to new forms of cancer therapies [3,4,5]
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