Abstract
Cutaneous malignant melanomas share a number of molecular attributes such as limitless replicative potential that define capabilities acquired by most malignancies. Accordingly, much effort has been focused on evaluating and validating protein markers related to these capabilities to function as melanoma prognostic markers. However, a few studies have also highlighted the prognostic value of markers that define melanocytic differentiation and the plasticity of melanoma cells to trans-differentiate along several other cellular pathways. Here, we provide a comprehensive review and evaluation of the prognostic significance of melanocyte-lineage markers such as MITF and melanogenic proteins, as well as markers of vascular epithelial and neuronal differentiation.
Highlights
The incidence of cutaneous malignant melanoma, the deadliest skin cancer, is increasing rapidly
Despite the impressive progress made in understanding of molecular mechanisms involved in melanoma tumorigenesis, management of patients diagnosed with primary cutaneous melanoma remains a challenge due to the lack of reliable prognostic markers
Based on the survey of literature and our own published data, we believe that there is a need for critical evaluation of differentiation and trans-differentiation markers as prognostic markers
Summary
The incidence of cutaneous malignant melanoma, the deadliest skin cancer, is increasing rapidly. The widely used evidence-based current system of Cancers 2010, 2 clinical staging, which is known as tumor-node-metastasis (TNM) classification, was developed based on analysis of 17,600 melanoma patients and was revised recently to incorporate improved understanding of the disease and analysis of additional patients [2,3]. According to this system, tumor thickness (Breslow thickness) and ulceration are the most powerful predictors of survival in patients with localized stage I and II melanomas. We summarize and critically examine the published literature on genes and proteins related to melanoma differentiation and trans-differentiation as prognostic markers and potential targets for therapy
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