Prognostic importance of mitochondrial markers in mucosal and cutaneous head and neck melanomas

• Published in: Human pathology Vol. 85; pp. 279 - 289
• Main Authors: Soares, Ciro Dantas, Morais, Thayná Melo de Lima, Carlos, Roman, de Almeida, Oslei Paes, Mariano, Fernanda Viviane, Altemani, Albina, de Carvalho, Maria Goretti Freire, Corrêa, Marcelo Brum, dos Reis, Rodrigo Ribas Dias, Amorim, Luciana Schultz, Jorge, Jacks
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-03-2019; Elsevier Limited
• Subjects: Cell cycle; Cutaneous melanomas; FIS1; Head & neck cancer; Head and neck melanomas; Immunoglobulins; Medical prognosis; Melanoma; Metastasis; MFN2; Mitochondria; Morphology; Mucosal melanomas; Phosphorylation; Prognosis; Statistical methods; Studies; Surgery; Tumorigenesis; Tumors; FIS1; Mitochondria; Prognosis; Mucosal melanomas; MFN2; Head and neck melanomas; Cutaneous melanomas
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2018.11.009

Mitochondrial dysfunction is caused by an imbalance in the fission and fusion processes, and it has been implicated in the pathogenesis of several human cancers. However, the role of mitochondrial markers in melanomas still remains poorly understood. In this study, the authors assessed the expression of 3 mitochondrial markers (antimitochondrial, fission protein 1 [FIS1], and mitofusin 2 [MFN2]) in a series of head and neck mucosal and cutaneous melanomas. Patients with cutaneous (n = 56) and mucosal (oral, n = 30, sinonasal, n = 26) melanomas of the head and neck region were enrolled in this study. Clinical and follow-up data were retrieved from medical records. The expression of 3 mitochondrial markers was assessed by the immunohistochemistry, and then digitally quantified and correlated with clinicopathological data and outcome information. In the multivariate model, high mitochondrial content was identified as an independent prognostic value for disease-free survival (DFS) in cutaneous melanomas and overall survival in oral melanomas. FIS1 expression was significantly associated with lower overall survival rates in patients with oral melanomas and strictly correlated with vascular invasion in mucosal melanomas. MFN2 was associated with high risk of distant metastasis in patients with cutaneous melanomas. In summary, the authors demonstrated that mitochondrial content, along with FIS1 and MFN2 expressions, is correlated with important clinicopathological characteristics in patients with cutaneous and mucosal head and neck melanomas.
•High content of mitochondria may play an important role in melanoma pathogenesis.•FIS1 expression predicts lower overall survival rates in oral melanoma patients.•FIS1 expression is associated with vascular invasion in mucosal melanoma patients.•MFN2 expression predicts metastasis in cutaneous melanoma patients.