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Epidemiology and Biological Features of Melanoma
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Epidemiology and Biological Features of Melanoma

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Epidemiology and Prevention".

Deadline for manuscript submissions: closed (23 September 2022) | Viewed by 38490

Special Issue Editors

Prof. Dr. Ludwig M. Heindl

E-Mail Website
Guest Editor
1. Department of Ophthalmology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany
2. Center for Integrated Oncology (CIO) Aachen-Bonn-Cologne-Duesseldorf, Cologne, Germany
Interests: malignant melanoma; eyelid melanoma; conjunctival melanoma; uveal melanoma; ophthalmic oncology; ophthalmic plastic and reconstructive surgery
Prof. Dr. Jochen Sven Utikal

E-Mail Website
Co-Guest Editor
1. Skin Cancer Unit, German Cancer Research Center (DKFZ), 69121 Heidelberg, Germany
2. Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim, Ruprecht-Karl University of Heidelberg, 68167 Mannheim, Germany
Interests: skin cancer; malignant melanoma; translational research; stem cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Malignant melanomas arising from pigment-producing melanocytes have shown an increasing incidence in recent years. Melanocytes are predominantly found in the skin and eyes, and to a lesser extent in other tissues throughout the body. Exposure to sunlight is considered the main risk factor for genetic mutations and the subsequent malignant transformation from benign melanocytes to malignant melanoma. The most common type of melanoma is the cutaneous melanoma, which accounts for over 90% of all melanomas, while the ocular melanoma accounts for about 5% of all melanomas. In this Special Issue, we will publish original research articles and reviews providing new insights into the epidemiology and biology of malignant melanomas.

Prof. Dr. Ludwig M. Heindl
Prof. Dr. Jochen Sven Utikal
Guest Editors

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • melanoma
  • malignant melanoma
  • skin melanoma
  • conjunctival melanoma
  • uveal melanoma
  • epidemiology
  • genetics
  • signaling pathways
  • biology

Published Papers (17 papers)

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14 pages, 975 KiB  
Article
Phenotypic and Dermoscopic Patterns of Familial Melanocytic Lesions: A Pilot Study in a Third-Level Center
by Gabriele Roccuzzo, Silvia Giordano, Thomas Granato, Francesco Cavallo, Luca Mastorino, Gianluca Avallone, Barbara Pasini, Pietro Quaglino and Simone Ribero
Cancers 2023, 15(15), 3772; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15153772 - 25 Jul 2023
Cited by 1 | Viewed by 922
Abstract
Cutaneous melanoma is a highly aggressive skin cancer. It is estimated that 5% to 10% of the underlying mutations are hereditary and responsible for familial (or hereditary) melanoma. These patients are prone to the early development and higher risk of multiple melanomas. In [...] Read more.
Cutaneous melanoma is a highly aggressive skin cancer. It is estimated that 5% to 10% of the underlying mutations are hereditary and responsible for familial (or hereditary) melanoma. These patients are prone to the early development and higher risk of multiple melanomas. In recent years, an increasing number of genes have been identified thanks to genetic testing, allowing the subsequent surveillance of individuals at risk, yet it is still difficult to predict the presence of these mutations on a clinical basis. In this scenario, specific phenotypic and dermoscopic features could help clinicians in their identification. The aim of this work has been to correlate mutations to prevalent dermoscopic patterns, paving the way for reference models useful in clinical practice. In our cohort, out of 115 patients referred to genetic counseling for melanoma, 25 tested positive (21.7%) for critical mutations: CDKN2A (n = 12), MITF (n = 3), BAP1 (n = 1), MC1R (n = 3), PTEN (n = 1), TYR (n = 2), OCA2 (n = 1), and SLC45A2 (n = 2). The phenotype profiles obtained through the digital acquisition, analysis, and description of both benign and malignant pigmented lesions showed a predominance of the type II skin phenotype, with an elevated mean total nevus number (182 moles, range 75–390). As for dermoscopic features, specific mutation-related patterns were described in terms of pigmentation, areas of regression, and vascular structures. Although further studies with larger cohorts are needed, our work represents the beginning of a new approach to the study and diagnosis of familial melanoma, underlining the importance of clinical and dermoscopic patterns, which may constitute a reference model for each gene, enabling comparison. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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13 pages, 1390 KiB  
Article
Lack of Influence of Non-Overlapping Mutations in BRAF, NRAS, or NF1 on 12-Month Best Objective Response and Long-Term Survival after Checkpoint Inhibitor-Based Treatment for Metastatic Melanoma
by Alyssa Panning, Wolfram Samlowski and Gabriel Allred
Cancers 2023, 15(13), 3527; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15133527 - 07 Jul 2023
Cited by 2 | Viewed by 1657
Abstract
Background: Non-overlapping somatic mutations in BRAF, NRAS, or NF1 genes occur in 85% of metastatic melanoma patients. It is not known whether these mutations affect immunotherapy outcome. Materials and methods: Next-Gen sequencing of 324 oncogenes was performed in 73 metastatic melanoma patients. A [...] Read more.
Background: Non-overlapping somatic mutations in BRAF, NRAS, or NF1 genes occur in 85% of metastatic melanoma patients. It is not known whether these mutations affect immunotherapy outcome. Materials and methods: Next-Gen sequencing of 324 oncogenes was performed in 73 metastatic melanoma patients. A retrospective review of immunotherapy outcome was performed. Results: BRAF fusions/internal rearrangements, BRAF V600E, NRAS, NF1 mutations, and triple-negative genotypes occurred in 6.9%, 30.1%, 17.8%, 32.9%, and 12.3% of patients, respectively. Median potential follow-up was 41.0 months. Patients with BRAF fusion/rearrangement had decreased progression-free and overall survival (p = 0.015). The other genotypes each had similar progression-free and overall survival. Patients who achieved a complete best objective response at 12 months (n = 36, 49.3%) were found to have significantly improved survival compared those who failed to achieve remissions (n = 37, 50.7%, p < 0.001). Conclusions: The most important determinant of long-term survival was achievement of a complete response by 12 months following immunotherapy. PR and SD were not a stable type of response and generally resulted in progression and death from melanoma. Rare patients with BRAF fusions or rearrangements had decreased progression-free and overall survival following initial immunotherapy. Other BRAF, NRAS, or NF1 mutations were not associated with significant differences in outcome. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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24 pages, 1311 KiB  
Article
Sun-Protective Clothing Worn Regularly during Early Childhood Reduces the Number of New Melanocytic Nevi: The North Queensland Sun-Safe Clothing Cluster Randomized Controlled Trial
by Simone L. Harrison, Petra G. Buettner and Madeleine J. Nowak
Cancers 2023, 15(6), 1762; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15061762 - 14 Mar 2023
Cited by 3 | Viewed by 2113
Abstract
Numerous pigmented moles are associated with sun exposure and melanomarisk. This cluster randomized controlled trial aimed to determine if sun-protective clothing could prevent a significant proportion of the moles developing in young children (ACTRN12617000621314; Australian New Zealand Clinical Trials Registry. Twenty-five childcare centers [...] Read more.
Numerous pigmented moles are associated with sun exposure and melanomarisk. This cluster randomized controlled trial aimed to determine if sun-protective clothing could prevent a significant proportion of the moles developing in young children (ACTRN12617000621314; Australian New Zealand Clinical Trials Registry. Twenty-five childcare centers in Townsville (19.25° S), Australia, were matched on shade provision and socioeconomic status. One center from each pair was randomized to the intervention arm and the other to the control arm. Children at 13 intervention centers wore study garments and legionnaire hats at childcare and received sun-protective swimwear and hats for home use, while children at the 12 control centers did not. The 1–35-month-old children (334 intervention; 210 control) were examined for moles at baseline (1999–2002) and were re-examined annually for up to 4 years. Both groups were similar at baseline. Children at intervention centers acquired fewer new moles overall (median 12.5 versus 16, p = 0.02; 0.46 versus 0.68 moles/month, p = 0.001) and fewer new moles on clothing-protected skin (6 vs. 8; p = 0.021 adjusted for confounding and cluster sampling) than controls. Intervention children had 24.3% fewer new moles overall (26.5 versus 35) and 31.6% (13 versus 19) fewer moles on clothing-protected skin than controls after 3.5 years. Sunlight’s influence on nevogenesis is mitigated when children regularly wear UPF 30-50+ clothing covering half their body, implying that increased clothing cover reduces melanoma risk. Sun-protective clothing standards should mandate reporting of the percentage of garment coverage for childrenswear. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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13 pages, 2982 KiB  
Article
Melanoma of the Scalp and Neck: A Population-Based Analysis of Survival and Treatment Patterns
by Matteo Scampa, Vladimir Mégevand, Juan A. Viscardi, Salvatore Giordano, Daniel F. Kalbermatten and Carlo M. Oranges
Cancers 2022, 14(24), 6052; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14246052 - 08 Dec 2022
Cited by 1 | Viewed by 1802
Abstract
Introduction: Melanoma is an aggressive skin cancer. Large demographic and clinic-pathologic studies are required to identify variations of tumour behavior. The aim of our study was to offer updated epidemiologic data on the scalp and neck melanoma with an overall survival analysis. Method: [...] Read more.
Introduction: Melanoma is an aggressive skin cancer. Large demographic and clinic-pathologic studies are required to identify variations of tumour behavior. The aim of our study was to offer updated epidemiologic data on the scalp and neck melanoma with an overall survival analysis. Method: The SEER database was searched for all scalp and neck melanoma in adult patients between 2000 and 2019. Demographic and clinic-pathologic variables were described. Their impact on overall survival was assessed with the log-rank test after Kaplan–Meier model. A multivariable cox-regression was conducted to identify predictors of decreased survival. A p-value of <0.005 was considered statistically significant. Results: 20,728 Melanomas of the scalp and neck were identified. Mean age was 62.5 years. Gender ratio was 76.3% males. 79% of the tumours were localized at diagnosis. Increasing age, male gender, tumour ulceration, high mitotic rate or nodular subtype were independent prognostic factors of decreased overall survival. Surgery with less than 1 cm margin is associated with the best overall survival in this cohort. No significant difference in OS was seen between less than 1 cm and 1 to 2 cm margins. Conclusion: Knowledge of negative prognostic factors might help identify subgroups at risk and adapt their oncologic treatment. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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12 pages, 1229 KiB  
Article
Melanoma of the Upper Limb and Shoulder: A Surveillance, Epidemiology, and End Results Analysis of Epidemiology and Survival 2000–2019
by Solange N. Walz, Jérôme Martineau, Matteo Scampa, Daniel F. Kalbermatten and Carlo M. Oranges
Cancers 2022, 14(22), 5672; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14225672 - 18 Nov 2022
Cited by 3 | Viewed by 2056
Abstract
(1) Background: Melanoma is the most common life-threatening cancer among skin cancers. Almost all locations of the skin can be affected by melanoma, and the upper limbs are one of the most frequent locations. We aimed to study the epidemiology and survival outcomes [...] Read more.
(1) Background: Melanoma is the most common life-threatening cancer among skin cancers. Almost all locations of the skin can be affected by melanoma, and the upper limbs are one of the most frequent locations. We aimed to study the epidemiology and survival outcomes of patients with melanoma localized in the upper extremities compared with other sites. (2) Methods: The National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database is considered the most representative of the U.S. population; we extracted melanoma cases diagnosed between 2000 and 2019. Several characteristics, including demographical, pathological, and therapeutic, were recorded, and upper extremity melanomas and melanomas from other areas were compared. Overall survival was assessed, and the groups were compared. (3) Results: 69,436 patients had melanoma in the upper limbs and shoulders and 204,794 in other body parts. Overall, 35,267 patients with upper extremity melanoma were males, 34,169 were females, and the mean age was 60. For the rest of the body, there were 118,654 males and 86,140 females, with a mean age of 59. Surgery alone was the most commonly used treatment, while radiation therapy was the least used for all sites. Women appear to have better survival than men. Superficial spreading melanoma is the least lethal subtype, while nodular melanoma is the most dangerous. (4) Conclusion: Women under 50 are more at risk than men of the same age. The trend reverses after age 50 where men are at greater risk. In addition to gender and age, disease stage and major histologic subtypes influence survival. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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18 pages, 4462 KiB  
Article
The Anti-Vascular Endothelial Growth Factor Receptor 1 (VEGFR-1) D16F7 Monoclonal Antibody Inhibits Melanoma Adhesion to Soluble VEGFR-1 and Tissue Invasion in Response to Placenta Growth Factor
by Maria Grazia Atzori, Claudia Ceci, Federica Ruffini, Manuel Scimeca, Rosella Cicconi, Maurizio Mattei, Pedro Miguel Lacal and Grazia Graziani
Cancers 2022, 14(22), 5578; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14225578 - 14 Nov 2022
Cited by 3 | Viewed by 1136
Abstract
Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family involved in tumor-associated angiogenesis and melanoma invasion of the extra-cellular matrix (ECM) through activation of membrane VEGF receptor 1 (VEGFR-1). A soluble VEGFR-1 (sVEGFR-1) form is released in [...] Read more.
Placenta growth factor (PlGF) is a member of the vascular endothelial growth factor (VEGF) family involved in tumor-associated angiogenesis and melanoma invasion of the extra-cellular matrix (ECM) through activation of membrane VEGF receptor 1 (VEGFR-1). A soluble VEGFR-1 (sVEGFR-1) form is released in the ECM, where it sequesters proangiogenic factors and stimulates endothelial or tumor cell adhesion and chemotaxis through interaction with α5β1 integrin. The anti-VEGFR-1 monoclonal antibody (D16F7 mAb) inhibits VEGF-A or PlGF-mediated signal transduction without affecting ligand interaction, thus preserving sVEGFR-1 decoy function. The aim of this study was to investigate whether D16F7 mAb hampers melanoma spread by in vitro analysis of cell adhesion to sVEGFR-1, ECM invasion, transmigration through an endothelial cell monolayer and in vivo evaluation of tumor infiltrative potential in a syngeneic murine model. Results indicate that D16F7 mAb significantly inhibits melanoma adhesion to sVEGFR-1 and ECM invasion, as well as transmigration in response to PlGF. Moreover, treatment of melanoma-bearing mice with the anti-VEGFR-1 mAb not only inhibits tumor growth but also induces a significant reduction in bone infiltration associated with a decrease in PlGF-positive melanoma cells. Furthermore, D16F7 mAb reduces PlGF production by melanoma cells. Therefore, blockade of PLGF/VEGFR-1 signaling represents a suitable strategy to counteract the metastatic potential of melanoma. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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16 pages, 4848 KiB  
Article
Exercise Promotes Pro-Apoptotic Ceramide Signaling in a Mouse Melanoma Model
by Jonghae Lee, Hannah Savage, Shinji Maegawa, Riccardo Ballarò, Sumedha Pareek, Bella Samia Guerrouahen, Vidya Gopalakrishnan and Keri Schadler
Cancers 2022, 14(17), 4306; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14174306 - 02 Sep 2022
Cited by 3 | Viewed by 1762
Abstract
Ceramides are essential sphingolipids that mediate cell death and survival. Low ceramide content in melanoma is one mechanism of drug resistance. Thus, increasing the ceramide content in tumor cells is likely to increase their sensitivity to cytotoxic therapy. Aerobic exercise has been shown [...] Read more.
Ceramides are essential sphingolipids that mediate cell death and survival. Low ceramide content in melanoma is one mechanism of drug resistance. Thus, increasing the ceramide content in tumor cells is likely to increase their sensitivity to cytotoxic therapy. Aerobic exercise has been shown to modulate ceramide metabolism in healthy tissue, but the relationship between exercise and ceramide in tumors has not been evaluated. Here, we demonstrate that aerobic exercise causes tumor cell apoptosis and accumulation of pro-apoptotic ceramides in B16F10 but not BP melanoma models using mice. B16F10 tumor-bearing mice were treated with two weeks of moderate treadmill exercise, or were control, unexercised mice. A reverse-phase protein array was used to identify canonical p53 apoptotic signaling as a key pathway upregulated by exercise, and we demonstrate increased apoptosis in tumors from exercised mice. Consistent with this finding, pro-apoptotic C16-ceramide, and the ceramide generating enzyme ceramide synthase 6 (CerS6), were higher in B16F10 tumors from exercised mice, while pro-survival sphingosine kinase 1 (Sphk1) was lower. These data suggest that exercise contributes to B16F10 tumor cell death, possibly by modulating ceramide metabolism toward a pro-apoptotic ceramide/sphingosine-1-phosphate balance. However, these results are not consistent in BP tumors, demonstrating that exercise can have different effects on tumors of different patient or mouse origin with the same diagnosis. This work indicates that exercise might be most effective as a therapeutic adjuvant with therapies that kill tumor cells in a ceramide-dependent manner. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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14 pages, 2391 KiB  
Article
Characteristics, Treatments, and Survival of Uveal Melanoma: A Comparison between Chinese and American Cohorts
by Jingting Luo, Chengkai Zhang, Yuhang Yang, Jingying Xiu, Hanqing Zhao, Chuqiao Liang, Zhaoxun Feng, Yuning Chen, Yueming Liu, Yang Li and Wenbin Wei
Cancers 2022, 14(16), 3960; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14163960 - 17 Aug 2022
Cited by 4 | Viewed by 1648
Abstract
Uveal melanoma (UM) is the most common intraocular malignant carcinoma. This study aimed to compare the clinical features, treatment modalities, and prognosis of UM patients in China with those in America over a 15-year period. In the study, 4088 American patients with primary [...] Read more.
Uveal melanoma (UM) is the most common intraocular malignant carcinoma. This study aimed to compare the clinical features, treatment modalities, and prognosis of UM patients in China with those in America over a 15-year period. In the study, 4088 American patients with primary UM from the Surveillance, Epidemiology, and End Results (SEER) database and 1508 Chinese patients from Tongren-ophthalmology Research Association of Clinical Evaluation (TRACE) were included. Univariable and multivariable analyses were performed to determine prognostic factors and propensity score matching (PSM) and sensitivity analyses were applied to adjust for confounders and identify independent prognostic factors. Chinese patients were diagnosed at a younger age (mean ± SD, 47.3 ± 12.5 years vs. 59.7 ± 14.8 years) and tumors at diagnosis were larger (diameter: 12.0 ± 3.54 mm vs. 11.3 ± 8.27 mm; thickness: 7.13 ± 3.28 mm vs. 4.91 ± 3.01 mm). Chinese patients were more likely to undergo brachytherapy than American patients. Chinese patients had better overall survival than American patients while no significant differences exhibited after adjusting for age through PSM. In conclusion, compared with American patients, Chinese patients had younger onset age, larger tumors at diagnosis and better prognosis, mainly because of their younger age. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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18 pages, 2623 KiB  
Article
ADCK2 Knockdown Affects the Migration of Melanoma Cells via MYL6
by Marlene Vierthaler, Qian Sun, Yiman Wang, Tamara Steinfass, Juliane Poelchen, Thomas Hielscher, Daniel Novak, Viktor Umansky and Jochen Utikal
Cancers 2022, 14(4), 1071; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14041071 - 20 Feb 2022
Cited by 11 | Viewed by 2394
Abstract
Background: ADCK2 is a member of the AarF domain-containing kinase family, which consists of five members, and has been shown to play a role in CoQ metabolism. However, ADCKs have also been connected to cancer cell survival, proliferation and motility. In this study, [...] Read more.
Background: ADCK2 is a member of the AarF domain-containing kinase family, which consists of five members, and has been shown to play a role in CoQ metabolism. However, ADCKs have also been connected to cancer cell survival, proliferation and motility. In this study, we investigated the role of ADCK2 in melanoma. Methods: The effect of ADCK2 on melanoma cell motility was evaluated by a scratch assay and a transwell invasion assay upon siRNA-mediated knockdown or stable overexpression of ADCK2. Results: We found that high levels of intratumoral ADCK2 and MYL6 are associated with a higher survival rate in melanoma patients. Knocking down ADCK2 resulted in enhanced cell migration of melanoma cells. Moreover, ADCK2-knockdown cells adopted a more dedifferentiated phenotype. A gene expression array revealed that the expression of ADCK2 correlated with the expressions of MYL6 and RAB2A. Knocking down MYL6 in ADCK2-overexpressing cells could abrogate the effect of ADCK2 overexpression and thus confirm the functional connection between ADCK2 and MYL6. Conclusion: ADCK2 affects melanoma cell motility, most probably via MYL6. Our results allow the conclusion that ADCK2 could act as a tumor suppressor in melanoma. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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19 pages, 6383 KiB  
Article
Expression of Autoimmunity-Related Genes in Melanoma
by Francesca Scatozza and Antonio Facchiano
Cancers 2022, 14(4), 991; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14040991 - 16 Feb 2022
Cited by 1 | Viewed by 2226
Abstract
(1) Background. Immune response dysregulation plays a key role in melanoma, as suggested by the substantial prognosis improvement observed under immune-modulation therapy. Similarly, the role of autoimmunity is under large investigation in melanoma and other cancers. (2) Methods. Expression of 98 autoimmunity-related genes [...] Read more.
(1) Background. Immune response dysregulation plays a key role in melanoma, as suggested by the substantial prognosis improvement observed under immune-modulation therapy. Similarly, the role of autoimmunity is under large investigation in melanoma and other cancers. (2) Methods. Expression of 98 autoimmunity-related genes was investigated in 1948 individuals (1024 melanoma and 924 healthy controls). Data were derived from four independent databases, namely, GEO in the selection phase, and Ist Online, GEPIA2 and GENT2, in three sequential validation-steps. ROC analyses were performed to measure the ability to discriminate melanoma from controls. Principal Component Analysis (PCA) was used to combine expression data; survival analysis was carried out on the GEPIA2 platform. (3) Results. Expression levels of NOD2, BAX, IL-18 and ADRB2 were found to be significantly different in melanoma vs. controls and discriminate melanoma from controls in an extremely effective way, either as single molecules (AUC > 0.93 in all cases) or as a profile, according to the PCA analysis. Patients showing high-expression of NOD2 and of IL-18 also show a significant survival improvement as compared to low-expression patients. (4) Conclusions. Four genes strongly related to autoimmunity show a significant altered expression in melanoma samples, highlighting the role they may play in melanoma. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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10 pages, 268 KiB  
Article
Epidemiology and Molecular Profile of Mucosal Melanoma: A Population-Based Study in Southern Europe
by Anna Carbó-Bagué, Jordi Rubió-Casadevall, Montserrat Puigdemont, Arantza Sanvisens, Glòria Oliveras, Mònica Coll, Bernat del Olmo, Ferran Perez-Bueno and Rafael Marcos-Gragera
Cancers 2022, 14(3), 780; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14030780 - 03 Feb 2022
Cited by 9 | Viewed by 2400
Abstract
Background: Mucosal melanoma is a rare neoplasm on which few epidemiological population-based studies have been published. A good surgical approach is the standard treatment, but the prognosis is worse than that of skin melanoma. The analysis of mucosal melanoma’s mutational profile can help [...] Read more.
Background: Mucosal melanoma is a rare neoplasm on which few epidemiological population-based studies have been published. A good surgical approach is the standard treatment, but the prognosis is worse than that of skin melanoma. The analysis of mucosal melanoma’s mutational profile can help to develop target therapies in advanced disease or adjuvant settings. Methods: We analyzed the database of the Cancer Registry of Girona, a region located in the north-east of Spain, in the period of 1994–2018. We selected cases of primary invasive melanoma, excluding those located in the skin, eye, central nervous system and an unknown primary site. Epidemiological analysis included incidence and survival. Mutational profile analysis was performed with a custom gene panel. Results: Forty-two patients were identified: 14 (33%) had vulvar-vaginal melanoma, 15 (35.7%) had rectal melanoma, 12 (28.6%) had melanoma located in the head and neck sphere and 1 male patient had a urethral melanoma. European age-standardized incidence rates for vulvar-vaginal, rectal and head and neck melanoma were 0.09, 0.1 and 0.09 cases/100,000 inhabitant-years, respectively. Five-year observed survival rates were 37.5%, 20% and 25% for these types of cancers. NRAS Q61 was the most frequent mutation found. Conclusion: Our study confirms the steady incidence and low survival of mucosal melanomas in a region of southern Europe. NRAS and NF1 play a role in the molecular landscape of mucosal melanoma. MEK and PI3K/mTOR inhibitors could be reasonable treatment options and are being studied in clinical trials. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
27 pages, 8183 KiB  
Article
Canine Oral Melanoma Genomic and Transcriptomic Study Defines Two Molecular Subgroups with Different Therapeutical Targets
by Anais Prouteau, Stephanie Mottier, Aline Primot, Edouard Cadieu, Laura Bachelot, Nadine Botherel, Florian Cabillic, Armel Houel, Laurence Cornevin, Camille Kergal, Sébastien Corre, Jérôme Abadie, Christophe Hitte, David Gilot, Kerstin Lindblad-Toh, Catherine André, Thomas Derrien and Benoit Hedan
Cancers 2022, 14(2), 276; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14020276 - 06 Jan 2022
Cited by 3 | Viewed by 3268
Abstract
Mucosal melanoma (MM) is a rare, aggressive clinical cancer. Despite recent advances in genetics and treatment, the prognosis of MM remains poor. Canine MM offers a relevant spontaneous and immunocompetent model to decipher the genetic bases and explore treatments for MM. We performed [...] Read more.
Mucosal melanoma (MM) is a rare, aggressive clinical cancer. Despite recent advances in genetics and treatment, the prognosis of MM remains poor. Canine MM offers a relevant spontaneous and immunocompetent model to decipher the genetic bases and explore treatments for MM. We performed an integrative genomic and transcriptomic analysis of 32 canine MM samples, which identified two molecular subgroups with a different microenvironment and structural variant (SV) content. The overexpression of genes related to the microenvironment and T-cell response was associated with tumors harboring a lower content of SVs, whereas the overexpression of pigmentation-related pathways and oncogenes, such as TERT, was associated with a high SV burden. Using whole-genome sequencing, we showed that focal amplifications characterized complex chromosomal rearrangements targeting oncogenes, such as MDM2 or CDK4, and a recurrently amplified region on canine chromosome 30. We also demonstrated that the genes TRPM7, GABPB1, and SPPL2A, located in this CFA30 region, play a role in cell proliferation, and thus, may be considered as new candidate oncogenes for human MM. Our findings suggest the existence of two MM molecular subgroups that may benefit from dedicated therapies, such as immune checkpoint inhibitors or targeted therapies, for both human and veterinary medicine. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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13 pages, 1148 KiB  
Article
Immune Checkpoint Inhibitor Treatment and Ophthalmologist Consultations in Patients with Malignant Melanoma or Lung Cancer—A Nationwide Cohort Study
by Maria D’Souza, Mette Bagger, Mark Alberti, Morten Malmborg, Morten Schou, Christian Torp-Pedersen, Gunnar Gislason, Inge Marie Svane and Jens Folke Kiilgaard
Cancers 2022, 14(1), 49; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14010049 - 23 Dec 2021
Cited by 2 | Viewed by 2110
Abstract
Purpose: To estimate the frequency of first-time ocular events in patients treated with immune checkpoint inhibitors (ICI). Methods: Patients with cancer in 2011–2018 in Denmark were included and followed. The outcomes were first-time ophthalmologist consultation and ocular inflammation. One-year absolute risks of outcomes [...] Read more.
Purpose: To estimate the frequency of first-time ocular events in patients treated with immune checkpoint inhibitors (ICI). Methods: Patients with cancer in 2011–2018 in Denmark were included and followed. The outcomes were first-time ophthalmologist consultation and ocular inflammation. One-year absolute risks of outcomes and hazard ratios were estimated. Results: 112,289 patients with cancer were included, and 2195 were treated with ICI. One year after the first ICI treatment, 6% of the patients with cancer, 5% and 8% of the lung cancer (LC) and malignant cutaneous melanoma (MM) patients, respectively, had a first-time ophthalmologist consultation. The risk of ocular inflammation was 1% (95% confidence interval (CI) 0.4–1.2). Among patients with MM, ICI was associated with ocular inflammation in women (HR 12.6 (95% CI 5.83–27.31) and men (4.87 (95% CI 1.79–13.29)). Comparing patients with and without ICI treatment, the risk of first-time ophthalmologist consultation was increased in patients with LC (HR 1.74 (95% CI 1.29–2.34) and MM (HR 3.21 (95% CI 2.31–4.44). Conclusions: The one-year risks of first-time ophthalmologist consultation and ocular inflammation were 6% and 1%, respectively, in patients treated with ICI. In patients with LC and MM, the risk was increased in patients with ICI compared with patients without ICI. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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Review

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20 pages, 2676 KiB  
Review
Ethanol Metabolism and Melanoma
by Zili Zhai, Takeshi Yamauchi, Sarah Shangraw, Vincent Hou, Akiko Matsumoto and Mayumi Fujita
Cancers 2023, 15(4), 1258; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15041258 - 16 Feb 2023
Cited by 4 | Viewed by 1794
Abstract
Malignant melanoma is the deadliest form of skin cancer. Despite significant efforts in sun protection education, melanoma incidence is still rising globally, drawing attention to other socioenvironmental risk factors for melanoma. Ethanol and acetaldehyde (AcAH) are ubiquitous in our diets, medicines, alcoholic beverages, [...] Read more.
Malignant melanoma is the deadliest form of skin cancer. Despite significant efforts in sun protection education, melanoma incidence is still rising globally, drawing attention to other socioenvironmental risk factors for melanoma. Ethanol and acetaldehyde (AcAH) are ubiquitous in our diets, medicines, alcoholic beverages, and the environment. In the liver, ethanol is primarily oxidized to AcAH, a toxic intermediate capable of inducing tumors by forming adducts with proteins and DNA. Once in the blood, ethanol and AcAH can reach the skin. Although, like the liver, the skin has metabolic mechanisms to detoxify ethanol and AcAH, the risk of ethanol/AcAH-associated skin diseases increases when the metabolic enzymes become dysfunctional in the skin. This review highlights the evidence linking cutaneous ethanol metabolism and melanoma. We summarize various sources of skin ethanol and AcAH and describe how the reduced activity of each alcohol metabolizing enzyme affects the sensitivity threshold to ethanol/AcAH toxicity. Data from the Gene Expression Omnibus database also show that three ethanol metabolizing enzymes (alcohol dehydrogenase 1B, P450 2E1, and catalase) and an AcAH metabolizing enzyme (aldehyde dehydrogenase 2) are significantly reduced in melanoma tissues. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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50 pages, 674 KiB  
Review
Genetics and RNA Regulation of Uveal Melanoma
by Cristina Barbagallo, Michele Stella, Giuseppe Broggi, Andrea Russo, Rosario Caltabiano and Marco Ragusa
Cancers 2023, 15(3), 775; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers15030775 - 26 Jan 2023
Cited by 8 | Viewed by 2464
Abstract
Uveal melanoma (UM) is the most common intraocular malignant tumor and the most frequent melanoma not affecting the skin. While the rate of UM occurrence is relatively low, about 50% of patients develop metastasis, primarily to the liver, with lethal outcome despite medical [...] Read more.
Uveal melanoma (UM) is the most common intraocular malignant tumor and the most frequent melanoma not affecting the skin. While the rate of UM occurrence is relatively low, about 50% of patients develop metastasis, primarily to the liver, with lethal outcome despite medical treatment. Notwithstanding that UM etiopathogenesis is still under investigation, a set of known mutations and chromosomal aberrations are associated with its pathogenesis and have a relevant prognostic value. The most frequently mutated genes are BAP1, EIF1AX, GNA11, GNAQ, and SF3B1, with mutually exclusive mutations occurring in GNAQ and GNA11, and almost mutually exclusive ones in BAP1 and SF3B1, and BAP1 and EIF1AX. Among chromosomal aberrations, monosomy of chromosome 3 is the most frequent, followed by gain of chromosome 8q, and full or partial loss of chromosomes 1 and 6. In addition, epigenetic mechanisms regulated by non-coding RNAs (ncRNA), namely microRNAs and long non-coding RNAs, have also been investigated. Several papers investigating the role of ncRNAs in UM have reported that their dysregulated expression affects cancer-related processes in both in vitro and in vivo models. This review will summarize current findings about genetic mutations, chromosomal aberrations, and ncRNA dysregulation establishing UM biology. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
24 pages, 1531 KiB  
Review
Melanoma Management: From Epidemiology to Treatment and Latest Advances
by Joana Lopes, Cecília M. P. Rodrigues, Maria Manuela Gaspar and Catarina Pinto Reis
Cancers 2022, 14(19), 4652; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14194652 - 24 Sep 2022
Cited by 33 | Viewed by 5699
Abstract
Melanoma is the deadliest skin cancer, whose morbidity and mortality indicators show an increasing trend worldwide. In addition to its great heterogeneity, melanoma has a high metastatic potential, resulting in very limited response to therapies currently available, which were restricted to surgery, radiotherapy [...] Read more.
Melanoma is the deadliest skin cancer, whose morbidity and mortality indicators show an increasing trend worldwide. In addition to its great heterogeneity, melanoma has a high metastatic potential, resulting in very limited response to therapies currently available, which were restricted to surgery, radiotherapy and chemotherapy for many years. Advances in knowledge about the pathophysiological mechanisms of the disease have allowed the development of new therapeutic classes, such as immune checkpoint and small molecule kinase inhibitors. However, despite the incontestable progress in the quality of life and survival rates of the patients, effectiveness is still far from desired. Some adverse side effects and resistance mechanisms are the main barriers. Thus, the search for better options has resulted in many clinical trials that are now investigating new drugs and/or combinations. The low water solubility of drugs, low stability and rapid metabolism limit the clinical potential and therapeutic use of some compounds. Thus, the research of nanotechnology-based strategies is being explored as the basis for the broad application of different types of nanosystems in the treatment of melanoma. Future development focus on challenges understanding the mechanisms that make these nanosystems more effective. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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Other

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16 pages, 2147 KiB  
Systematic Review
A Meta-Analysis on the Impact of the COVID-19 Pandemic on Cutaneous Melanoma Diagnosis in Europe
by Konstantinos Seretis, Nikolaos Bounas, Georgios Gaitanis and Ioannis Bassukas
Cancers 2022, 14(24), 6085; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14246085 - 10 Dec 2022
Cited by 6 | Viewed by 1353
Abstract
The COVID-19 pandemic has been the epicenter of healthcare attention globally for the past two years, and large-scale adaptations in healthcare provision have been required. This study aimed to investigate the impact of the pandemic and the resulting lockdowns on cutaneous melanoma diagnosis [...] Read more.
The COVID-19 pandemic has been the epicenter of healthcare attention globally for the past two years, and large-scale adaptations in healthcare provision have been required. This study aimed to investigate the impact of the pandemic and the resulting lockdowns on cutaneous melanoma diagnosis and tumor burdens in Europe. A relevant literature search in electronic databases was conducted from inception to September 2022. The inclusion criteria were: controlled studies published in a peer-reviewed journal evaluating cutaneous melanoma in Europe and reporting data on melanoma characteristics from diagnoses. The quality of studies was evaluated using the Cochrane ROBINS-I tool for assessing bias in non-randomized studies. Meta-analysis was conducted utilizing a random effects model to synthesize the data. A total of 25 studies involving 32,231 patients were included in the data analysis models. Statistically significant increases in mean Breslow thickness (0.29 mm (0.03–0.55 mm)), ulceration rates (OR = 1.66 (1.29–2.13)), and resultant tumor staging were observed in the PostCovid group, with subgroup analysis revealing that lockdown-derived data were responsible for this trend. This meta-analysis reported on the impact of COVID-19 restrictions on melanoma diagnosis in Europe, emphasizing the higher tumor burden and disease progression state provoked by healthcare adaptations in the pandemic period. Full article
(This article belongs to the Special Issue Epidemiology and Biological Features of Melanoma)
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