Nevi, dysplastic nevi, and melanoma

Abstract

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. BRAF V600E 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, BRAF V600E 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 p15 INK4b , p16 INK4a , 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.

Nevus Variations in the Jordanian Population: Effects of Age, Medical Conditions, Environment, Congenital, Inherited, and Genetic Factors

“…This particular scenario can disrupt the senescence status, potentially allowing the progression of nevi into dysplastic nevi or melanoma. 34 …”

Study on the Potential Antitumor Activity of Cookies Enriched with Sambucus nigra L., Aronia melanocarpa, Hippophae rhamnoides L., and Crataegus L., on WM793 Melanoma and MCF-7 Breast Cell Lines

“…Among the risk factors, 30% of breast cancer cases are attributed to an inappropriate lifestyle, including improper diet leading to excess body weight, lack of physical activity, or alcohol consumption. Despite the unfavorable prognosis in later stage disease, mainly due to metastasis, the recommended treatment in both cases, melanoma and breast cancer, is immunotherapy in combination with other chemotherapeutic drugs [23,29]. Chemotherapy drugs are used for treating people with an advanced cancer or after surgery.…”

Cellular senescence in skin‐related research: Targeted signaling pathways and naturally occurring therapeutic agents

“…Therefore, senescence evasion is an important part of melanoma pathogenesis (Leclerc et al, 2017, Sung & Chang, 2022. To sum up, the role of cellular senescence in carcinogenesis is complex, and further research is needed to elucidate it.…”

“…Nonetheless, oncogenic mutations appear insufficient to cause malignant transformation (Damsky & Bosenberg, 2017 ; Leclerc et al, 2017 ). Naevi cells are characterized by senescence markers such as SA‐β‐Gal, phosphatase, and tensin homolog (PTEN) or p16 INK4a expression, resulting in growth arrest (Gray‐Schopfer et al, 2006 ; Leclerc et al, 2017 ; MacKenzie Ross et al, 2013 ; Sung & Chang, 2022 ). It has also been reported that dysplastic naevi and early melanomas express less senescent markers (Gray‐Schopfer et al, 2006 ; MacKenzie Ross et al, 2013 ).…”

“…It has also been reported that dysplastic naevi and early melanomas express less senescent markers (Gray‐Schopfer et al, 2006 ; MacKenzie Ross et al, 2013 ). Therefore, senescence evasion is an important part of melanoma pathogenesis (Leclerc et al, 2017 , Sung & Chang, 2022 ). To sum up, the role of cellular senescence in carcinogenesis is complex, and further research is needed to elucidate it.…”