Aetiology and Pathogenesis of Cutaneous Melanoma: Current Concepts and Advances

Abstract

Melanoma develops from malignant transformations of the pigment-producing melanocytes. If located in the basal layer of the skin epidermis, melanoma is referred to as cutaneous, which is more frequent. However, as melanocytes are be found in the eyes, ears, gastrointestinal tract, genitalia, urinary system, and meninges, cases of mucosal melanoma or other types (e.g., ocular) may occur. The incidence and morbidity of cutaneous melanoma (cM) are constantly increasing worldwide. Australia and New Zealand are world leaders in this regard with a morbidity rate of 54/100,000 and a mortality rate of 5.6/100,000 for 2015. The aim of this review is to consolidate and present the data related to the aetiology and pathogenesis of cutaneous melanoma, thus rendering them easier to understand. In this article we will discuss these problems and the possible impacts on treatment for this disease.

Cutaneous Melanomas: A Single Center Experience on the Usage of Immunohistochemistry Applied for the Diagnosis

“…Cutaneous melanoma (cM) is a malignant and potentially lethal tumor that develops from the transformation of the melanocytes that normally reside in the basal layer of the skin epidermis and form with the keratinocytes the epidermal melanin unit [ 1 , 2 ]. The annual incidence and morbidity of cM are constantly increasing worldwide (the number of newly diagnosed cases has more than doubled since 1973), probably due to population aging, the increase of risk factors such as chronic sun damage, and the improvement of diagnostic tools; besides, unlike other malignancies, cM affects a higher proportion of younger patients (median age: 57 years), with a sex preponderance that varies in different age groups (female preponderance in younger age groups (4:10 in 20–30-year-olds); male preponderance (16:10 in >85-year-olds)) [ 3 , 4 ].…”

“…The appropriate and early diagnosis of cM is crucial for improving the prognosis and therapeutic strategies of the affected patients [ 3 , 4 ]. In this scenario, the immunohistochemistry, as an essential and indispensable aid to the correct histological diagnosis, plays a key role [ 1 , 2 , 3 , 4 ]. This review aims to present all the data related to the immunohistochemistry of cM, discussing their application for diagnosis, prognostic characterization, and treatment of this deadly disease, as well as briefly summarizing the role of these molecules in the biology of melanocytes and cM.…”

The Anticancer Potential of Doxycycline and Minocycline—A Comparative Study on Amelanotic Melanoma Cell Lines

“…The malignant transformation of melanocytes can be triggered by different environmental factors, including UV radiation, heavy metals, or pesticides. Moreover, geographical location, skin phototypes I and II, intermittent and intense sun exposure, numerous pigment nevi, genetic susceptibility, or immunosuppression also belong to risk factors for melanoma development [ 5 , 6 ]. The process of melanocyte transformation to melanoma cells is based on genetic and epigenetic changes.…”

Construction and Validation of a Ferroptosis-Related Prognostic Signature for Melanoma Based on Single-Cell RNA Sequencing

“…Mutations in the TP53 gene occur at a lower frequently in skin cancer compared with all human cancers ( Ribeiro Moura Brasil Arnaut et al, 2021 ; Scatena et al, 2021 ), indicating the potiential role of TP53 in the induction of ferroptosis. TP53 mutation is one of the most common mutations in UVR-induced DNA damage and leads to tumor initiation and progression ( Strashilov and Yordanov, 2021 ; Torrens-Mas et al, 2020 ). Although TP53 mutations are not common in melanoma, recent researches have revealed that UVR-induced p53 mutations are tightly associated with the increased incidence of melanoma ( Loureiro et al, 2020 ).…”