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

Hum Pathol. 2019 Mar:85:279-289. doi: 10.1016/j.humpath.2018.11.009. Epub 2018 Nov 20.

Abstract

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.

Keywords: Cutaneous melanomas; FIS1; Head and neck melanomas; MFN2; Mitochondria; Mucosal melanomas; Prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Disease-Free Survival
  • Female
  • GTP Phosphohydrolases / metabolism*
  • Head and Neck Neoplasms / metabolism*
  • Head and Neck Neoplasms / mortality
  • Head and Neck Neoplasms / pathology
  • Humans
  • Immunohistochemistry
  • Male
  • Melanoma / metabolism*
  • Melanoma / mortality
  • Melanoma / pathology
  • Membrane Proteins / metabolism*
  • Middle Aged
  • Mitochondria / metabolism*
  • Mitochondrial Proteins / metabolism*
  • Prognosis
  • Skin Neoplasms / metabolism*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • FIS1 protein, human
  • Membrane Proteins
  • Mitochondrial Proteins
  • GTP Phosphohydrolases
  • MFN2 protein, human