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Original Article
The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8+ T Cells
Hermin Aminah Usman, Bethy S. Hernowo, Maringan Diapari Lumban Tobing, Reti Hindritiani
J Pathol Transl Med. 2018;52(3):164-170.   Published online April 20, 2018
DOI: https://doi.org/10.4132/jptm.2018.04.04
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  • 6 Web of Science
  • 6 Crossref
AbstractAbstract PDF
Background
The tumor microenvironment including immune surveillance affects malignant melanoma (MM) behavior. Nuclear factor κB (NF-κB) stimulates the transcription of various genes in the nucleus and plays a role in the inflammatory process and in tumorigenesis. CD8+ T cells have cytotoxic properties important in the elimination of tumors. However, inhibitory receptors on the cell surface will bind to programmed death-ligand 1 (PD-L1), causing CD8+ T cells to lose their ability to initiate an immune response. This study analyzed the association of NF-κB and PD-L1 expression levels and CD8+ T-cell counts with depth of invasion of acral MM, which may be a predictor of aggressiveness related to an increased risk of metastasis.
Methods
A retrospective cross-sectional study was conducted in the Department of Anatomical Pathology, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin Hospital using 96 cases of acral melanoma. Immunohistochemical staining was performed on paraffin blocks using anti–NF-κB, –PD-L1, and -CD8 antibodies and invasion depth was measured using dotSlide-imaging software.
Results
The study showed significant associations between the individual expression of NF-κB and PD-L1 and CD8+ T-cell number, with MM invasion depth. NF-κB was found to be a confounding variable of CD8+ T-cell number (p < .05), but not for PD-L1 expression (p = .154). Through multivariate analysis it was found that NF-κB had the greatest association with the depth of invasion (p < .001), whereas PD-L1 was unrelated to the depth of invasion because it depends on the number of CD8+ T cells (p = .870).
Conclusions
NF-κB plays a major role in acral MM invasion, by decreasing the number of CD8+ T cells in acral MM.

Citations

Citations to this article as recorded by  
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    Hui-Min Liu, Ming-Yan Cheng, Meng-Han Xun, Zhi-Wei Zhao, Yun Zhang, Wei Tang, Jun Cheng, Jia Ni, Wei Wang
    International Journal of Molecular Sciences.2023; 24(4): 3755.     CrossRef
  • Clinical features, molecular pathology, and immune microenvironmental characteristics of acral melanoma
    Jianping Gui, Zhen Guo, Di Wu
    Journal of Translational Medicine.2022;[Epub]     CrossRef
  • High Expression of COX-2 Associated with the Depth of Invasion on Acral Melanoma by Increasing TGF-β1
    Nastassa Gipsyianti, Afiati Aziz, Bethy S Hernowo, Hermin A Usman
    Clinical, Cosmetic and Investigational Dermatology.2021; Volume 14: 209.     CrossRef
  • More than just acral melanoma: the controversies of defining the disease
    Sara S Bernardes, Ingrid Ferreira, David E Elder, Aretha B Nobre, Héctor Martínez‐Said, David J Adams, Carla Daniela Robles‐Espinoza, Patricia A Possik
    The Journal of Pathology: Clinical Research.2021; 7(6): 531.     CrossRef
  • CD103+ T Lymphocyte Count Linked to the Thickness of Invasion on Acral Melanoma without E-Cadherin Involvement
    Fauzan Ali Zainal Abidin, Hermin Aminah Usman, Sri Suryanti, Bethy S Hernowo
    Clinical, Cosmetic and Investigational Dermatology.2021; Volume 14: 1783.     CrossRef
  • Translational pathology, genomics and the development of systemic therapies for acral melanoma
    Yian Ann Chen, Jamie K. Teer, Zeynep Eroglu, Jheng-Yu Wu, John M. Koomen, Florian A. Karreth, Jane L. Messina, Keiran S.M. Smalley
    Seminars in Cancer Biology.2020; 61: 149.     CrossRef

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