Association of Nuclear VDR Immunoexpression with Breslow’s Thickness in Acral Melanoma

Fitria Sholihah, Hermin Aminah Usman, Birgitta Maria Dewayani

Abstract


Background: Acral melanoma (AM) is a subtype of malignant melanoma (MM) that has a predilection for glabrous skin and is the most common type of melanoma among Asians. Depth of invasion is one of the prognostic factors in AM. VDR may have an association with depth of invasion in AM. However, reports from Asian patients are still lacking. The aim of this study was to explore the association between VDR immunoexpression and depth of invasion in AM patients in Bandung, Indonesia.

Methods: This study was a retrospective cross-sectional study that analyzed the nuclear and cytoplasm VDR expression of melanoma cells and its association with Breslow’s thickness in patients with AM in Dr. Hasan Sadikin General Hospital Bandung. VDR immunostaining was performed on paraffin blocks. The Breslow thickness was measured using dot slide software. Chi square statistical analysis was done to determine the results.

Results: Of the 30 patients, 73% had a Breslow thickness of >4 mm.  There was a significant inverse association between nuclear VDR immunoexpression and Breslow thickness of AM (p<0.001), but not for cytoplasmic VDR immunoexpression (p=0.914). 

Conclusion: Low nuclear VDR immunoexpression is associated with the depth of invasion in AM. Nuclear VDR immunoexpression possibly affect progression and should be considered before administration of vitamin D therapy in AM.

 


Keywords


Acral melanoma, Breslow’s thickness, VDR

Full Text:

PDF

References


  1. Huang K, Xu Y, Gabriel EM, Misra S, Chen Y, Bagaria SP. Comparative analysis of acral melanoma in Chinese and Caucasian patients. J Skin Cancer. 2020;2020:5169051.
  2. Slominski AT, Brożyna AA, Zmijewski MA, Jóźwicki W, Jetten AM, Mason RS, et al. Vitamin D signaling and melanoma: role of vitamin D and its receptors in melanoma progression and management. Lab Invest. 2017;97(6):706–24.
  3. Del Puerto C, Navarrete-Dechent C, Molgó M, Borzutzky A, González S. Vitamin D axis and its role in skin carcinogenesis: a comprehensive review. Applied Cancer Res. 2016;36(1):5.
  4. Basurto‐Lozada P, Molina‐Aguilar C, Castaneda‐Garcia C, Vázquez‐Cruz ME, Garcia‐Salinas OI, Álvarez‐Cano A, et al. Acral lentiginous melanoma: basic facts, biological characteristics and research perspectives of an understudied disease. Pigment Cell Melanoma Res. 2021;34(1):59–71.
  5. Borkowska AM, Szumera-Ciećkiewicz A, Spałek MJ, Teterycz P, Czarnecka AM, Rutkowski PŁ. Clinicopathological features and prognostic factors of primary acral melanomas in Caucasians. J Clin Med. 2020;9(9):2996.
  6. Lee T-L, Lin M-H, Liao Y-H, Liau J-Y, Sheen Y-S. Clinicopathological characteristics and prognosis in significantly thick acral lentiginous melanoma in Taiwan. J Formos Med Assoc. 2021;121(11):2338–44.
  7. Lino-Silva LS, Zepeda-Najar C, Salcedo-Hernández RA, Martínez-Said H. Acral lentiginous melanoma: survival analysis of 715 cases. J Cutan Med Surg. 2019;23(1):38–43.
  8. Paolino G, Bekkenk M, Didona D, Eibenschutz L, Richetta A, Cantisani C, et al. Is the prognosis and course of acral melanoma related to site-specific clinicopathological features? Eur Rev Med Pharmacol Sci. 2016;20(5):842–8.
  9. Mao L, Qi Z, Zhang L, Guo J, Si L. Immunotherapy in acral and mucosal melanoma: current status and future directions. Front Immunol. 2021;12:680407.
  10. Elder DE, Barnhil R, Bastian BC, Cook MG, de la Fouchardière A, Gerami P, et al. Melanocytic tumours classification and the pathway concept. In: Elder DE, Massi D, Scolyer RA, Willemze R, editors. WHO classification of skin tumours. 4th Ed. Lyon, France: International Agency for Research on Cancer (IARC); 2018. p. 66–71.
  11. Brożyna AA, Jóźwicki W, Slominski AT. Decreased VDR expression in cutaneous melanomas as marker of tumor progression: new data and analyses. Anticancer Res. 2014;34(6):2735–43.
  12. Bikle DD. Vitamin D receptor, a tumor suppressor in skin. Can J Physiol Pharmacol. 2015;93(5):349–54.
  13. Bikle DD, Oda Y, Tu C-L, Jiang Y. Novel mechanisms for the vitamin D receptor (VDR) in the skin and in skin cancer. J Steroid Biochem Mol Biol. 2015;148:47–51.
  14. Brożyna AA, Jozwicki W, Janjetovic Z, Slominski AT. Expression of vitamin D receptor decreases during progression of pigmented skin lesions. Hum Pathol. 2011;42(5):618–31.
  15. Gershenwald JE, Scolyer RA. Melanoma staging: American Joint Committee on Cancer (AJCC) 8th Edition and beyond. Ann Surg Oncol. 2018;25(8):2105–10.
  16. Ombra MN, Paliogiannis P, Doneddu V, Sini MC, Colombino M, Rozzo C, et al. Vitamin D status and risk for malignant cutaneous melanoma: recent advances. Eur J Cancer Prev. 2017;26(6):532–41.
  17. La Marra F, Stinco G, Buligan C, Chiriacò G, Serraino D, Di Loreto C, et al. Immunohistochemical evaluation of vitamin D receptor (VDR) expression in cutaneous melanoma tissues and four VDR gene polymorphisms. Cancer Biol Med. 2017;14(2): -162–75.
  18. Dominguez LJ, Farruggia M, Veronese N, Barbagallo M. Vitamin D sources, metabolism, and deficiency: available compounds and guidelines for its treatment. Metabolites. 2021;11(4):255.
  19. Huang K, Fan J, Misra S. Acral lentiginous melanoma: incidence and survival in the United States, 2006-2015, an analysis of the SEER registry. J Surg Res. 2020;251:329–39.
  20. Bikle DD. Vitamin D metabolism and function in the skin. Mol Cell Endocrinol. 2011;347(1–2):80–9.
  21. Nair R, Maseeh A. Vitamin D: the “sunshine” vitamin. J Pharmacol Pharmacother. 2012;3(2):118–26.
  22. Brożyna AA, Hoffman RM, Slominski AT. Relevance of vitamin D in melanoma development, progression and therapy. Anticancer Res. 2020;40(1):473–89.
  23. Handono K, Tanuwijaya LK, Fitri LE, Kalim H. The correlation between serum concentration of vitamin D with vitamin D receptor expression and disease activity in Indonesian patients with systemic lupus erythematosus: preliminary study. J Trop Life Science. 2014;4(2):113–8.
  24. Chen Y, Zhang J, Ge X, Du J, Deb DK, Li YC. Vitamin D receptor inhibits nuclear factor κB activation by interacting with IκB kinase β protein. J Biol Chem. 2013;288(27):19450–8.
  25. Usman HA, Hernowo BS, Tobing MDL, Hindritiani R. The major role of NF-κB in the depth of invasion on acral melanoma by decreasing CD8+ T cells. J Pathol Transl Med. 2018;52(3):164–70.
  26. Sundar IK, Hwang J-W, Wu S, Sun J, Rahman I. Deletion of vitamin D receptor leads to premature emphysema/COPD by increased matrix metalloproteinases and lymphoid aggregates formation. Biochem Biophys Res Commun. 2011;406(1):127–33.
  27. Zamolo G, Grahovac M, Žauhar G, Vučinić D, Kovač L, Brajenić N, et al. Matrix metalloproteinases MMP‐1, MMP‐2, and MMP‐13 are overexpressed in primary nodular melanoma. J Cutaneous Pathol. 2020;47(2):139–45.
  28. Zmijewski MA, Carlberg C. Vitamin D receptor (s): in the nucleus but also at membranes? Exp Dermatol. 2020;29(9):876–84.




DOI: https://doi.org/10.15850/amj.v10n4.2801

Article Metrics

Abstract view : 162 times
PDF - 85 times


 This Journal indexed by

                  

          

 

Creative Commons License
AMJ is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

 


View My Stats