Abstract
BackgroundMelanoma is the major cause of skin cancer death worldwide. Parkinson's disease is a neurodegenerative disorder that is caused by mutation of α-synuclein or other genes. Importantly, epidemiological studies have reported co-occurrence of melanoma and Parkinson's disease, suggesting that these two diseases could share common genetic components.Methodology/Principal FindingsRecently, we found that human melanoma cell lines highly express α-synuclein, whereas the protein is undetectable in the non-melanoma cancer cell lines tested. To investigate the expression of α-synuclein in human melanoma tissues, we immunostained sections of melanoma, nevus, non-melanocytic cutaneous carcinoma, and normal skin. α-Synuclein was positively detected in 86% of the primary and 85% of the metastatic melanoma sections, as well as in 89% of nevus sections. However, α-synuclein was undetectable in non-melanocytic cutaneous carcinoma and normal skin.Conclusions/SignificanceThe Parkinson's disease-related protein, α-synuclein, is expressed in both malignant and benign melanocytic lesions, such as melanomas and nevi. Although α-synuclein cannot be used to distinguish between malignant and benign melanocytic skin lesions, it might be a useful biomarker for the diagnosis of metastatic melanoma.
Highlights
Malignant melanoma is the major cause of skin cancer mortality, and its incidence is rising worldwide [1,2]
A-synuclein is involved in the pathogenesis of Parkinson’s disease (PD), but its relationship with melanoma has been unknown
In a large-scale study including over 8,000 PD cases, a diagnosis of melanoma was associated with an approximately 50% increased risk of subsequently developing PD [10], whereas individuals with PD had a twofold increase in risk of subsequently developing melanoma [11]
Summary
Malignant melanoma is the major cause of skin cancer mortality, and its incidence is rising worldwide [1,2]. Histological biomarkers might help us to diagnose and identify patients with early-stage melanoma who are likely to develop advanced disease and would benefit from additional therapies [3]. S-100, HMB-45, and MART-1 are well known biomarkers for melanoma, and antibodies against these molecules have been used for immunostaining to diagnose malignant melanoma [4]. The anti-S-100 antibody demonstrates excellent sensitivity because the S-100 protein is expressed in almost all primary and metastatic malignant melanomas. MART-1 has been reported to be more specific and more sensitive than HMB-45 in both primary and metastatic melanoma [4,7,8]. Epidemiological studies have reported co-occurrence of melanoma and Parkinson’s disease, suggesting that these two diseases could share common genetic components
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