J Pathol Transl Med.  2018 May;52(3):164-170. 10.4132/jptm.2018.04.04.

The Major Role of NF-κB in the Depth of Invasion on Acral Melanoma by Decreasing CD8⁺ T Cells

• Usman HA
• Hernowo BS
• Tobing MD
• Hindritiani R

• KMID: 2412928
• DOI: http://doi.org/10.4132/jptm.2018.04.04

Abstract

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.

Keyword

Acral; CD8⁺ T cells; Invasion; Melanoma; NF-κB; PD-L1

MeSH Terms

Antibodies
Carcinogenesis
Confounding Factors (Epidemiology)
Cross-Sectional Studies
Melanoma*
Multivariate Analysis
Neoplasm Metastasis
Paraffin
Pathology
Retrospective Studies
T-Lymphocytes*
Tumor Microenvironment
Antibodies
Paraffin

Figure

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  Fig. 1. Positive immunoexpression of nuclear factor κB on acral malignant melanoma.

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  Fig. 2. Immunoexpression of progammed death-ligand1 ≥ 5% on acral malignant melanoma.

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  Fig. 3. CD8+ T cell number ≥25 by immunohistochemistry on acral malignant melanoma.

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