Tzu-Chi Medical Journal (Jan 2022)

Nevi, dysplastic nevi, and melanoma: Molecular and immune mechanisms involving the progression

  • Wei-Wen Sung,
  • Chung-Hsing Chang

DOI
https://doi.org/10.4103/tcmj.tcmj_158_20
Journal volume & issue
Vol. 34, no. 1
pp. 1 – 7

Abstract

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Melanocytic nevi, dysplastic nevi, and melanoma are all derived from the pigment-producing cells, namely melanocytes. Concerning the clinical spectrum, cutaneous melanoma is the most aggressive skin cancer with a low survival rate, while nevi are the most common benign lesions in the general population, and dysplastic nevi place in between nevi and melanoma. Ultraviolet (UV) radiation is a well-recognized extrinsic risk factor for all three. BRAFV600E is a well-recognized driver mutation that activates the RAS-BRAF-mitogen-activated protein kinase (MAPK) signaling pathway among 40%–60% of melanoma cases. Interestingly, BRAFV600E mutation is detected even more in acquired nevi, approximately 80%. However, in nevi, several tumor suppressors such as p53 and phosphatase and tensin homolog (PTEN) are intact, and senescence factors, including p15INK4b, p16INK4a, p19, and senescence-associated acidic β-galactosidase, are expressed, leading to cell senescence and cell cycle arrest. Although loss of p53 function is rarely found in melanoma, decreased or loss of PTEN with an activated PI3k/Akt signaling pathway is common in nevi, which may abolish senescence status and allow further progression into dysplastic nevi or melanoma. At present, mouse models closely resembling human nevi are used for investigating these phenomena. Melanocortin 1 receptor deficiency, an intrinsic risk factor for melanomagenesis, is related to the production of procarcinogenic pheomelanin and the inhibition of PTEN function. Immune response escape via programmed cell death-1/programmed cell death ligand-1 interaction plays further roles in monitoring the spectrum. Here, we review the current literature on the molecular and immune mechanisms involving the transition from benign nevi to malignant melanoma.

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