背景:头颈部粘膜黑素瘤(MMs)是罕见的肿瘤,与更常见的皮肤肿瘤(皮肤黑素瘤-CMs)相比,具有不良预后和较差的预后。很少有研究比较线粒体动态标志物在这些肿瘤中的表达。这项研究旨在评估线粒体标记与黑色素瘤进展的相关性,以及它们作为淋巴结受累和远处转移的预测因子的潜力。
方法:抗线粒体(AMT)的免疫组织化学,动力蛋白相关蛋白1(DRP1),线粒体裂变蛋白1(FIS1),mitofusin-1(MFN1),在112例头颈部CM和MM中进行了mitofusin-2(MFN2)抗体检测。Cox回归多变量模型用于评估AMT的相关性,考虑淋巴结和远处转移的风险,FIS1和MFN2的表达。
结果:研究的所有标记在肿瘤细胞中的染色高于正常邻近组织。MM中的线粒体含量高于CM,它与口腔黑色素瘤的淋巴结转移密切相关。FIS1和DRP1表达式都与CM中Clark的高级水平有关,它们在口腔黑素瘤中过度表达。此外,MFN2的免疫表达增加与CM的转移风险显着相关,它在鼻窦黑色素瘤中也过表达。
结论:我们的结果表明,线粒体分裂和融合过程在皮肤和粘膜黑素瘤的肿瘤发生和淋巴结和远处转移的发展过程中可以发挥重要作用。
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.