Dysplastic nevus: Fact and fiction

Rosendahl, Cliff; Grant‐Kels, Jane M.; Que, Syril Keena T.

doi:10.1016/j.jaad.2015.04.029

Cited by 50 publications

(33 citation statements)

References 44 publications

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“…The incidence of malignant melanoma shows a constant increase, particularly in the Caucasian population, worldwide during the past decades (Holmes, ; Nikolaou and Stratigos, ). The major risk factors are exposure to ultraviolet radiation, high nevus counts, large nevus size, and genetic predisposition (Marks, ; Rosendahl et al., ). Although the mechanism of transformation is incompletely characterized, histological examinations have demonstrated that melanocytic nevi precursors can be identified in between 26 and 58% of cutaneous melanomas (Sagebiel, ; Tsao et al., ).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of tubulin β‐3 as a novel senescence‐associated gene in melanocytic malignant transformation

Orfanidis

Wäster

Lundmark

et al. 2017

Pigment Cell Melanoma Res

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Evaluation of tubulin β-3 as a novel senescence-associated gene in melanocytic malignant transformation., Pigment Cell & Melanoma Research, 2017. 30(2) SummaryMalignant melanoma might develop from melanocytic nevi in which the growth-arrested state has been broken. We analyzed the gene expression of young and senescent human melanocytes in culture and compared the gene expression data with a dataset from nevi and melanomas. A concordant altered gene expression was identified in 84 genes when comparing the growth-arrested samples with proliferating samples. TUBB3, which encodes the microtubule protein tubulin β-3, showed a decreased expression in senescent melanocytes and nevi and was selected for further studies. Depletion of tubulin β-3 caused accumulation of cells in the G2/M phase and decreased proliferation and migration.Immunohistochemical assessment of tubulin β-3 in benign lesions revealed strong staining in the superficial part of the intradermal components, which faded with depth. In contrast, primary melanomas exhibited staining without gradient in a disordered pattern and strong staining of the invasive front. Our results describe an approach to find clinically useful diagnostic biomarkers to more precisely identify cutaneous malignant melanoma and present tubulin β-3 as a candidate marker. SignificanceThe development and progression of a melanocytic nevus into a malignant melanoma is characterized by alteration of gene expression and growth promoting signaling to break the growth-arrested state. By combining the gene expression profiles from skin lesions and cell culture models, we identify candidate biomarkers that distinguish malignant melanoma from benign melanocytic lesions. Tubulin β-3 may have a diagnostic impact in melanoma.Running title: Tubulin β-3 expression in nevi and melanomas

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Section: Introductionmentioning

confidence: 99%

Evaluation of tubulin β‐3 as a novel senescence‐associated gene in melanocytic malignant transformation

Orfanidis

Wäster

Lundmark

et al. 2017

Pigment Cell Melanoma Res

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“…So far, re‐excision of HDN have not yet been shown to decrease incidence of melanoma. The value or necessity of excising these lesions must be carefully evaluated and data is limited but currently suggest that HDN can be safely observed with minimal adverse patient outcomes . Ultimately a large‐scale randomized control trial would be the ideal study in order to ascertain the utility of re‐excision vs. observation.…”

Section: Discussionmentioning

confidence: 99%

Surgical re-excision vs. observation for histologically dysplastic naevi: a systematic review of associated clinical outcomes

et al. 2018

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“…Rosendahl et al examine the current data, which suggest that this entity exists as histologically and possibly genetically different from common nevus, with some overlapping features. Studies show that a melanoma associated with a nevus is just as likely to arise in a common nevus as in dysplastic nevus [7].…”

Section: Genesis Of Melanomamentioning

confidence: 99%

Possibilities for the Therapy of Melanoma: Current Knowledge and Future Directions

Valko-Rokytovská¹,

Simkova²,

Milkovičová³

et al. 2018

Human Skin Cancers - Pathways, Mechanisms, Targets and Treatments

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This chapter presents an overview of possibilities for the therapy of melanoma, current knowledge and future direction. Skin cancer is one of the most frequent types of cancers. Melanoma is much less common than basal cell and squamous cell skin cancers, but it is far more dangerous. Detailed knowledge of melanoma at the molecular level allows to develop new treatment alternatives and to design effective new drugs. There are two approaches in therapy of melanoma in the present based on immunotherapy and targeted therapy or their combination. Immunotherapy includes immune checkpoint blockades, whereas targeted therapy is represented by protein kinase inhibitors, such as BRAF inhibitors, MEK inhibitors, and NRAS inhibitors. Detailed knowledge of protein structure and the understanding of its role in key signaling pathways in melanoma development lead to the designation of new protein kinase inhibitors in targeted therapy.The incidence of melanoma is increasing at one of the highest rates of any form of cancer in fair-skinned populations around the world. The exposure to sunlight during the past 50 years is an important factor for the increasing incidence of melanoma. Mortality rates of melanoma show stabilization in Australia, in North America, and also in European countries. Prevention campaigns aim on reducing incidence and achieving earlier diagnosis, which resulted in an ongoing trend toward thin melanoma since the last two decades. However, the impact of primary prevention measures on incidence rates of melanoma is unlikely to be seen in the near future; rather, increasing incidence rates to 40-50/100,000 inhabitants/year should be expected in Europe in the next decades [15]. The possible signs and symptoms of melanomaThe possible signs and symptoms of melanoma are new moles or spots on the surface of skin that are changing in size, shape and color. Another important sign is a spot that looks different from all of the other spots on skin. There are the ABCDE criteria for these signs, which guide to the usual signs of melanoma:A -Asymmetry; one half of a nevi or birthmark does not match the other.B -Border; the edges are irregular, jagged, or blurred.C -Color; the color is not the same all over and may include shades of brown or black, or sometimes with patches of pink, red, white, or blue. D -Diameter; the spot is larger than 6 mm across, although melanomas can sometimes be smaller than this. E -Evolving; the nevi are changing in size, shape, or color. Melanoma classification and stagingThe classification schemes Breslow's thickness (depth) and Clark's level have been developed based on either the vertical thickness of the lesion in millimeters or the anatomic level of invasion of the layers of skin. Breslow's depth is considered significant factor in predicting the progression of the melanoma. Increased tumor thickness is correlated with metastasis and poorer prognosis. Tumors are classified into four categories based on the depth: thickness of 0.75 mm or less, thickness of 0.76-1.5 mm, thickness of 1.51-4 mm...

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Dysplastic nevus: Fact and fiction

Cited by 50 publications

References 44 publications

Evaluation of tubulin β‐3 as a novel senescence‐associated gene in melanocytic malignant transformation

Evaluation of tubulin β‐3 as a novel senescence‐associated gene in melanocytic malignant transformation

Surgical re-excision vs. observation for histologically dysplastic naevi: a systematic review of associated clinical outcomes

Possibilities for the Therapy of Melanoma: Current Knowledge and Future Directions

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