High Expression of COX-2 Associated with the Depth of Invasion on Acral Melanoma by Increasing TGF-β1

Abstract

Introduction Acral melanoma (AM) has a poor prognosis since it is easily metastatic and resistant to chemo and immunotherapy. Cyclooxygenase-2 (COX-2) is an enzyme that plays a role in the carcinogenesis process. The increased expression of COX-2 has an impact on increasing levels of Myeloid-Derived Suppressor Cell (MDSC), which is a key regulator of immune. The increase in MDSC produces Transforming Growth Factor β1 (TGF-β1), which will suppress Natural Killer (NK) cells and Dendritic Cells (DC) function so that tumor cells are spared from the immune systems and are easier to invade surrounding tissues. Purpose This study aimed to determine the role of COX-2 and TGF-β1 on the depth of invasion on AM. Materials and Methods This study was a cross-sectional observational study on 40 paraffin blocks of AM cases during 2014–2019 in the Department of Pathology Anatomy, Faculty of Medicine, Dr. Hasan Sadikin General Hospital, Bandung. The depth of invasion of all samples was measured by dotSlide imaging software and the immunohistochemical staining of COX-2 and TGF-β1 was performed. The association between COX-2 and TGF-β1 expression and AM depth of invasion were analyzed using Mann Whitney. Results The result showed a significant association between COX-2 and TGF-β1 expression and depth of invasion on AM. COX-2 expression had a significant association with TGF-β1 expression (0.0001). Through multivariate analysis, it was found that COX-2 had the greatest association with the depth of invasion (p=0.0001). Conclusion The findings showed that increasing expression of COX-2 in AM is associated with the depth of invasion by increasing TGF-β1 and it might play important roles during the invasion process of AM.

High Immunoexpression of COX-2 as a Metastatic Risk Factor in ccRCC without PD-L1 Involvement

“…6 These findings are consistent with the research of Gipsyianti et al, which revealed high COX-2 immunoexpression in acral melanoma; Szlendak et al on colorectal adenocarcinoma; and Liu et al on renal cell carcinoma. 3,20,21 The results of the present show a significant association between COX-2 immunoexpression and the occurrence of metastases in ccRCC (p=0.001) with a POR of 10.28. These results indicate that ccRCC patients with high COX-2 immunoexpression are ten-times as likely to be associated with metastases as ccRCC patients with low COX-2 immunoexpression.…”

“…6 These findings are consistent with the research of Gipsyianti et al, which revealed high COX-2 immunoexpression in acral melanoma; Szlendak et al on colorectal adenocarcinoma; and Liu et al on renal cell carcinoma. 3 , 20 , 21 …”

Phenolic acids and a static magnetic field change the expression of transforming growth factor β isoforms in amelanotic melanoma cells

“…The research was carried out in terms of the role of the zinc finger protein ZNF224 in signaling the TGFβ pathway as a stimulator of the pro-oncogenic function of TGFβ favourable to epithelial-mesenchymal transition [ 9 ]. Moreover, Gipsyianti et al [ 35 ] noted the participation of both TGFβ and cyclooxygenase- 2 (COX-2) in the development of acral melanoma (AM), as well as the depth and invasion of the lesion. The involvement of the TGFβ pathway in the development of melanoma has also been noted by Ren et al [ 36 ].…”

CD103+ T Lymphocyte Count Linked to the Thickness of Invasion on Acral Melanoma without E-Cadherin Involvement

“…This develops because PGE2 eliminates the expression of CD127 on the surface of CD8+ T lymphocytes, decreasing their role as immunological surveillance and their capacity to proliferate. 12 TGF-β1, on the other hand, acts as an immunosuppressor by decreasing the activity of CD8+ T cells, NK cells, and dendritic cells. 23 In the end, the number of CD103+ T cells will decrease because the total number of CD8+ T cells is reduced since it is known that only CD8+ T cells express intratumor CD103+ T cells.…”