Expression of mitochondrial dynamics markers during melanoma progression: Comparative study of head and neck cutaneous and mucosal melanomas

Abstract

Background Head and neck mucosal melanomas (MMs) are rare tumors with adverse outcomes and poorer prognoses than their more common cutaneous counterparts (cutaneous melanomas—CMs). Few studies have compared the expression of mitochondrial dynamic markers in these tumors. This study aimed to assess the correlations of mitochondrial markers with melanoma progression and their potential as predictors of lymph node involvement and distant metastasis. Methods Immunohistochemistry against anti‐mitochondrial (AMT), dynamin‐related protein 1 (DRP1), mitochondrial fission protein 1 (FIS1), mitofusin‐1 (MFN1), and mitofusin‐2 (MFN2) antibodies was performed in 112 cases of head and neck CM and MM. A Cox regression multivariate model was used to assess the correlation of AMT, FIS1, and MFN2 expressions considering the risk for nodal and distant metastasis. Results All markers studied presented higher staining in tumor cells than normal adjacent tissues. Higher mitochondrial content was observed in MM than in CM, and it was significantly associated with nodal metastasis in oral melanomas. Both FIS1 and DRP1 expressions were related to advanced Clark's levels in CM, and they were overexpressed in oral melanomas. Moreover, increased immunoexpression of MFN2 was significantly associated with a higher risk of metastasis in CM, and it was also overexpressed in sinonasal melanomas. Conclusions Our results suggest that mitochondrial fission and fusion processes can play an important role during multiple stages of tumorigenesis and the development of nodal and distant metastasis in cutaneous and mucosal melanomas.

Drp1 expression levels correlate with clinical stage in extramammary Paget’s disease

“…3 In malignant melanomas, the Drp1 overexpression increased with progress through the clinical stages. 7 The present study showed similar results for EMPD as well as other malignancies. At the point of the signalling pathway, mTOR is one of the main regulators of cell proliferation and angiogenesis in EMPD.…”

“…6 Elderly patients have many factors associated with poor prognosis such as thick tumours, ulceration and male gender. [7][8][9] However, age retained its significance as an independent predictor of poor prognosis. 7 Several new drugs for metastatic melanoma have recently been approved for its use as adjuvant therapies in patients with resected stage III and IV melanoma.…”

“…[7][8][9] However, age retained its significance as an independent predictor of poor prognosis. 7 Several new drugs for metastatic melanoma have recently been approved for its use as adjuvant therapies in patients with resected stage III and IV melanoma. 10 However, the trials that led to the approval of these drugs did not include patients with stage IIB-IIC disease, even though their prognosis, is worse than that of patients with stage IIIA disease.…”

Bromodomain‐containing protein 4 inhibitor JQ1 promotes melanoma cell apoptosis by regulating mitochondrial dynamics

“… 39 Soares et al demonstrated that increased MFN2 expression in melanoma is significantly positively correlated with lymph node involvement and distant metastasis. 40 In this study, we found that JQ1 treatment significantly increased the expression of mitochondrial fission proteins and decreased the expression of fusion proteins in B16 cells. Mitochondrial fragmentation was observed by transmission electron microscopy, which is consistent with the increase in mitochondrial fission phenotypic characteristics.…”

<p>Contemporary Multidisciplinary Management of Sinonasal Mucosal Melanoma</p>

“…The former resulted in higher rates of vascular invasion in mucosal melanomas and the latter showed higher rates of distant metastasis, and both are responsible for reducing overall survival rates. 35,36 Treatment Paradigms for SNMM Surgery…”