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Objectives: To examine the rate of skin color reporting in randomized controlled trials (RCTs) involving melanoma in the top ten highest dermatology journals by impact factor over the past four decades., Methods: A systematic review of RCTs involving melanoma within the top ten dermatology journals, as determined by impact factor, was conducted from inception to July 10th, 2023. Studies were included if they reviewed the diagnosis and/or treatment of melanoma, were RCTs, directly involved patients and were written in English. Studies were characterized as positive for reporting skin of color (SOC) if the demographic data in the results or methods sections included any of the following: race, ethnicity, skin of color, Fitzpatrick scale, sunburn tendency, phototype, skin type, or skin tone., Results: Out of 76 studies initially identified, only 49 articles met inclusion criteria. Of these 49 articles, only 24 articles recorded data of skin color from their demographics (49%). Subgroup analysis showed no statistically significant difference in the rate of reporting between studies grouped by decade (p = 0.779) or by study location (p = 0.763)., Conclusion: Darker skin tones can disguise melanotic skin lesions. Less than 50% of RCTs related to melanoma in the top ten international dermatology journals included skin color within their results section to characterize study participants. This has a negative impact on our understanding of this potentially devastating disease., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Disclosures: Robert Brodell, M.D. discloses the following potential conflicts of interest: Advisory boards: Novan and Amgen. Research funding: Pfizer, Novartis, and Sanofi. Stock: Veragen, Inc. Deven P. Curtis, Natasha L. Salmen, Anthony N. Baumann, Justine F. Busby and Eliot N. Mostow have no conflicts to disclose., (© 2025. The Author(s).)

Background: Cutaneous malignant melanoma (CMM) is increasing in prevalence and possesses the highest mortality rate of any skin cancer. Positron Emission Tomography and Computed Tomography (PET-CT) may be utilised in either radiological staging or surveillance, primarily in stage III-IV disease. False positive (FP) results lead to patient distress, increased costs, and unnecessary follow-up. The FP rate in CMM literature varies widely, altering calculations of positive predictive value and has not undergone pooled meta-analytic., Materials and Methods: A systematic review and meta-analysis of FP results in prospective studies of PET-CT in CMM was performed in accordance with PRISMA guidelines., Results: The systematic review produced 14 trials for inclusion. Patient-based reporting had the lowest pooled proportion of FP results with 5.8 % (95 % CI = 3.3 % to 8.8 %), lesion-based was highest with 9.1 % (95 % CI = 3.4 % to 17.2 %) and combined was 6.1 % (95 % CI = 4.3 % to 8.1 %). Bias was low to unclear other than for FP reporting. Heterogeneity (I2) was variable across all analyses. FP findings were mainly lymphatic, dermatological, respiratory, or skeletal. Diagnostic information was not provided., Conclusions: This study was the first attempt to quantify the pooled proportion of FP results from PET-CT in CMM. A small number of studies (n = 14) were available due to the predominance of retrospective methodology. Due to inconsistent reporting the true proportion of FP results is unclear. Systemic distribution was expected but limited diagnostic information was provided. Repeat meta-analysis using retrospective work should be performed. Future work should be prospective with clearly documented FP proportion, distribution, diagnosis, and follow-up., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Basal cell carcinoma (BCC) is a slowly progressive, locally aggressive and rarely metastasizing cancer, and although its mortality is low, its morbidity and cost of disease are high. While BCC is more common, cutaneous malignant melanoma (CMM) is significant due to its higher mortality rate. These patients can be treated, but recurrence, metastasis and mortality may occur in such patients. Various environmental, phenotypic and genotypic factors, especially ultraviolet (UV) radiations, play a role in the etiology of BCC and CMM. Histopathological examination continues to be the "gold standard" in their diagnosis. Spexin (SPX) and DARS2 are newly discovered proteins linked to many diseases, including cancer. These proteins may have an effect on the development and expression of skin cancers such as BCC and CMM. In this study, we evaluated the potential of SPX and DARS2 expressions as immunohistochemical biomarkers in the differential diagnosis of BCC and CMM. This study was conducted retrospectively using samples taken from the pathology laboratory. A total of 180 patient samples were used. The control group consisted of healthy skin tissues of the patients, and the other groups consisted of BCC and CMM tissues of the same patients. Tissue samples of all three groups were evaluated immunohistochemically with SPX and DARS2. The immunoreactivity of SPX was found to be higher in BCC and CMM tissue samples than in healthy skin tissues in the control group. DARS2 immunoreactivity was found to be higher in CMM tissues compared to the other two groups, and statistically significant in BCC tissues when compared with healthy control group tissues. SPX can be used as an immunohistochemical biomarker in the diagnosis of BCC and CMM. Since DARS2 expression is statistically more significant in CMM tissues than in BCC tissues, it can be used in differential diagnosis., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background/aim: Over-expression of glucose transporters (GLUTs), membrane proteins that facilitate glucose transport, has been implicated in cutaneous melanomas. Our prior studies have demonstrated increased expression of GLUT1 and GLUT3 in melanomas and their association with poorer prognosis. This study aimed to investigate the expression of GLUT isoforms 4 and 8 in melanocytic lesions, examine the co-expression status of multiple GLUTs, and evaluate their prognostic significance., Materials and Methods: We analyzed 171 melanocytic lesions (97 primary melanomas, 19 metastatic melanomas, and 55 nevi) using a tissue microarray and immunohistochemistry using antibodies against GLUT4 and GLUT8. Membranous expression of GLUTs was scored using a semi-quantitative method. A combined GLUT total score was generated by summing scores from GLUT1, GLUT3, GLUT4, and GLUT8 (including data from previous studies)., Results: A significant up-regulation of GLUT4 and GLUT8 expression was found in melanomas compared to nevi (p<0.0001 for both). Concurrent over-expression of multiple GLUTs was more prevalent in melanomas compared to nevi (p<0.0001), and it was also more frequent in metastatic melanomas compared to primary melanomas (p=0.047). Importantly, high total GLUT expression scores were significantly correlated with negative prognostic factors, such as ulceration and mitoses (p=0.03 and p=0.008 respectively). Additionally, Kaplan-Meier survival curves revealed that patients with elevated GLUT total score in their melanomas had a lower disease-specific survival (p=0.006). Furthermore, analysis of multiple GLUTs improved diagnostic sensitivity., Conclusion: Similar to GLUT1 and GLUT3, melanoma exhibits up-regulation of GLUT 4 and GLUT8 compared to nevi. Evaluation of multiple GLUT isoforms improves diagnostic and prognostic values., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: In Italy, the incidence of cutaneous malignant melanoma is two-fold higher in the north than in the south. This gradient might be associated with differences in incidence trends and disease surveillance. We compared the time trends in incidence rates, mortality rates, dermatologic office visit rates and skin biopsy rates between the Emilia-Romagna Region (northern Italy) and the Sicily Region (southern Italy)., Methods: The cancer registries of Parma, Modena, Ferrara and Romagna (current population, 2,606,465) and Catania-Messina-Enna, Siracusa and Ragusa (2,775,019) provided incidence and mortality records for the years 2008-2017. The records of outpatient services delivered in public health facilities were obtained from the two Regional Administrations. Trends in rates were assessed with the estimated average annual percent change. North-south differences were expressed as age-standardised rate ratios., Results: In the context of a generalised increasing incidence trend, which was more moderate in the female population of the Sicily Region, the standardised rate ratios were: 5.31 (males) and 5.20 (females) for in situ cutaneous malignant melanoma; 2.10 and 2.07 for invasive cutaneous malignant melanoma, with an excess incidence concentrated in lesions ⩽1.00 mm thick (3.58 and 3.05); 3.00 and 2.44 for dermatologic office visits; and 5.25 and 5.02 for skin biopsies. Mortality was stable in both Regions., Conclusions: In the Emilia-Romagna Region, as compared with the Sicily Region, a higher incidence of cutaneous malignant melanoma -especially of in situ and early invasive cutaneous malignant melanoma- coexisted with a higher level of clinical surveillance. The question of the direction of the cause-effect relationship between increased incidence and increased diagnostic scrutiny remains open., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Observational studies have identified a dual effect of circulating inflammatory proteins and immune cells on cancer progression. However, the specific mechanisms of action have not been clarified in the exacerbation of cutaneous-origin tumors. Therefore, this study aims to investigate whether the causal relationship between circulating inflammatory factors and basal cell carcinoma (BCC), cutaneous malignant melanoma (SKCM), and cutaneous squamous cell carcinoma (cSCC) is regulated by immune cells., Methods: This study employed the Two-Sample Mendelian Randomization (TSMR) approach to investigate the causal relationships between 91 circulating inflammatory factors and three prevalent types of skin cancer from a genetic perspective. Bayesian Weighted Mendelian Randomization (BWMR) was also used to validate correlation and reverse MR to assess inverse relationships. Subsequent sensitivity analyses were conducted to limit the impact of heterogeneity and pleiotropy. Finally, the two-step Mendelian Randomization (two-step MR) method was utilized to ascertain the mediating effects of specific immune cell traits in the causal pathways linking circulating inflammatory factors with BCC, SKCM, and cSCC., Results: The Inverse Variance Weighted (IVW) method and the Bayesian Weighted Algorithm collectively identified nine inflammatory factors causally associated with BCC, SKCM, and cSCC. The results from Cochran's Q test, mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger intercept were not statistically significant (p < 0.05). Additionally, the proportions mediated by CD4+ CD8dim T cell %leukocyte, CD4-CD8-Natural Killer T %T cell, and CD20 on IgD-CD38-B cell for FIt3L, CCL4, and OSM were 9.26%, 8.96%, and 10.16%, respectively., Conclusion: Immune cell levels potentially play a role in the modulation process between circulating inflammatory proteins and cutaneous-origin exacerbated tumors. This finding offers a new perspective for the in-depth exploration of cutaneous malignancies., (© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.)

Background: Obesity is associated with chronic low-grade inflammation, which is linked to cancer development. Abdominal obesity (a body mass index, ABSI), however, has unusually been associated inversely with cutaneous malignant melanoma (CMM), while general obesity (body mass index, BMI) is associated positively. Leucocytes participate in inflammation and are higher in obesity, but prospective associations of leucocytes with cutaneous malignant melanoma are unclear., Methods: We examined the prospective associations of neutrophil, lymphocyte, and monocyte counts (each individually), as well as the prospective associations of ABSI and BMI, with cutaneous malignant melanoma in UK Biobank. We used multivariable Cox proportional hazards models and explored heterogeneity according to sex, menopausal status, age (≥ 50 years at recruitment), smoking status, ABSI (dichotomised at the median: ≥73.5 women; ≥79.8 men), BMI (normal weight, overweight, obese), and time to diagnosis., Results: During a mean follow-up of 10.2 years, 2174 CMM cases were ascertained in 398,450 participants. There was little evidence for associations with neutrophil or lymphocyte counts. Monocyte count, however, was associated inversely in participants overall (HR = 0.928; 95%CI: 0.888-0.971; per one standard deviation increase; SD = 0.144*10 9 /L women; SD = 0.169*10 9 /L men), specifically in older participants (HR = 0.906; 95%CI: 0.862-0.951), and more clearly in participants with low ABSI (HR = 0.880; 95%CI: 0.824-0.939), or with BMI ≥ 25 kg/m 2 (HR = 0.895; 95%CI: 0.837-0.958 for overweight; HR = 0.923; 95%CI: 0.848-1.005 for obese). ABSI was associated inversely in pre-menopausal women (HR = 0.810; 95%CI: 0.702-0.935; SD = 4.95) and men (HR = 0.925; 95%CI: 0.867-0.986; SD = 4.11). BMI was associated positively in men (HR = 1.148; 95%CI: 1.078-1.222; SD = 4.04 kg/m 2 ). There was little evidence for heterogeneity according to smoking status. The associations with monocyte count and BMI were retained to at least 8 years prior to diagnosis, but the association with ABSI was observed up to 4 years prior to diagnosis and not for longer follow-up time., Conclusions: Monocyte count is associated prospectively inversely with the risk of developing CMM in older individuals, while BMI is associated positively in men, suggesting a mechanistic involvement of factors related to monocytes and subcutaneous adipose tissue in melanoma development. An inverse association with ABSI closer to diagnosis may reflect reverse causality or glucocorticoid resistance., (© 2024. The Author(s).)

Background: Chronic inflammation has been shown to promote cancer progression. Rosacea is indeed a long-term inflammatory skin condition and had been reported to link with increased risk for several types of malignancies, but evidence for causality is lacking., Objectives: To systematically estimate the causal relationship between rosacea and several types of cancer, including cutaneous malignant melanoma (CMM), cutaneous squamous cell carcinoma (cSCC), basal cell carcinoma (BCC), actinic keratosis (AK), thyroid cancer, breast cancer, glioma and hepatic cancer, as well as explore the potential underlying pathogenesis., Methods: We conducted a bidirectional two-sample Mendelian randomization study to probe the potential causal relationships between rosacea and several types of cancer. Instrumental variables were established using genome-wide significant single nucleotide polymorphisms associated with rosacea and cancers. The assessment of causality was carried out through multiple methods, and the robustness of the results was evaluated via sensitivity analyses., Results: There was no significant indication of causal effects of rosacea on CMM (p ivw  = 0.71), cSCC (p ivw  = 0.45), BCC (p ivw  = 0.90), AK (p ivw  = 0.73), thyroid cancer (p ivw  = 0.59), glioma (p ivw  = 0.15), and hepatic cancer (p ivw  = 0.07), but the genetic risk of rosacea was associated with an increased susceptibility to human epidermal growth factor receptor (HER)-negative malignant neoplasm of breast (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.02-1.18; p ivw  = 0.01). TANK (TRAF family member associated nuclear factor kappa B (NFKB) activator) was identified as a common protective gene for both rosacea (OR, 0.90; 95% CI, 0.82-0.99; p ivw  = 0.048) and HER-negative malignant neoplasm of the breast (OR, 0.86; 95% CI, 0.75-0.98; p ivw  = 0.032), which was primarily enriched in the negative regulation of NF-κB signal transduction and may contribute to the genetic links between rosacea and this subtype of breast cancer., Conclusions: Our findings provide suggestive evidence for causal links between rosacea and HER-negative malignant neoplasm of the breast risk., (© 2024 The Authors. Skin Research and Technology published by John Wiley & Sons Ltd.)

Acral melanoma (AM) is the most common histologic subtype of melanoma in dark-skinned patients and is associated with a worse prognosis and a high mortality rate, largely due to the inconspicuous nature of early-stage lesions, which can lead to late diagnosis. Because of the overlapping clinical and histopathological features of AM with other forms of cutaneous melanomas, early detection of AM requires a multidisciplinary approach that integrates various diagnostic modalities, including clinical examination, dermoscopy, histopathology, molecular testing, radiological imaging, and blood tests. While surgery is the preferred method of treatment for AM, other therapeutic options may be employed based on the stage and underlying etiology of the disease. Immune checkpoint inhibitors, molecular targeted therapy, radiotherapy, chemotherapy, and oncolytic virotherapy represent promising advanced treatment options for AM. In this review, we provide an overview of the latest advancements in diagnostic and therapeutic methods for AM, highlighting the importance of early detection and the prompt, individualized management of this challenging disease.

Background: Tumor-associated macrophages (TAMs) are an immune component of the cutaneous malignant melanoma (CMM) microenvironment and affect tumor growth. TAMs can polarize into different phenotypes, that is, proinflammatory M1 and anti-inflammatory M2 macrophages. However, the role of the macrophage phenotype in CMM remains unclear., Methods: We examined 88 patients with CMM. Tissue microarrays were constructed, and the density of M1 and M2 macrophages was analyzed by immunohistochemistry. Immune cells coexpressing CD68 and phosphorylated signal transducer and activator of transcription 1 (pSTAT1) were considered M1 macrophages, whereas those coexpressing CD68 and c-macrophage activating factor (c-Maf) were defined as M2 macrophages. These TAMs were counted, and the relationships between the density of M1 and M2 macrophages and clinicopathological factors including prognosis were investigated., Results: The CD68/c-Maf score ranged from 0 to 34 (median: 5.5). The patients were divided based on the median score into the CD68/c-Maf high (≥5.5) and low (<5.5) expression groups. Univariate and multivariate analyses revealed that CD68/c-Maf expression was an independent predictive factor for progression-free survival and an independent prognostic factor for overall survival. CD68/pSTAT1 expression was found in only two patients., Conclusion: We suggest that CD68/pSTAT1 coexpression is rarely observed in patients with CMM, and high CD68/c-Maf expression is a predictor of worse prognosis in these patients., (© 2023 Wiley Periodicals LLC.)

Background: Cutaneous malignant melanoma (CMM) causes most skin cancer deaths in the United States (US). The mortality has been decreasing in the US population. We hypothesize that this population-level reduction is mainly attributable to the treatment advances, rather than the successful primary and secondary prevention., Methods: Using data from the Surveillance, Epidemiology, and End Results (SEER) databases, we collected the incidence, incidence-based mortality (IBM), and 5-year survival (5-YS) rates of CMM from 1994 to 2019. Trends by stage and sex were examined by joinpoint regression analyses and age-period-cohort analyses., Results: The overall incidence of CMM rose by 1.6% yearly from 1994 to 2006 (95% confidence interval [CI]: 0.9% to 2.2%) and then increased with a numerical trend. And we projected the incidence will continue to increase until 2029. In contrast, the IBM for all CMM has decreased yearly by 2.8% (95% CI: -3.9% to -1.8%) since 2010 after continuously increasing by 3.8% annually (95% CI: 3.2% to 4.4%) from 1996 to 2010. For early-stage (localized and regional) CMM, we found the incidence since 2005 plateaued without further increase, while the incidence for CMM at distant stage continuously increased by 1.4% per year (95% CI: 0.9% to 2.0%). Improvements in 5-YS were observed over the study period for all CMM and were most obvious in distant stage. And significant period effects were noted around the year 2010., Conclusion: This study demonstrated improved survival and reduced mortality of CMM at the US population level since 2010, which were consistent with the introduction of novel therapies. Encouraging effects of primary prevention among adolescents in the most recent cohorts were found. However, the plateaued overall incidence and early diagnosis rates indicated that advances in primary and secondary prevention are very much needed to further control the burden of CMM., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Cutaneous malignant melanoma (CMM) has the worst prognosis among skin cancers, especially metastatic CMM. Predicting its prognosis accurately could direct clinical decisions., Methods: The Surveillance, Epidemiology, and End Results database was screened to collect CMM patients' data. According to diagnosed time, patients were subdivided into three cohorts, train cohort (diagnosed between 2010 and 2013), validation cohort (diagnosed in 2014), and test cohort (diagnosed in 2015). Train cohort was used to train deep learning survival model for cutaneous malignant melanoma (DeepCMM). DeepCMM was then evaluated in train cohort and validation cohort internally, and validated in test cohort externally., Results: DeepCMM showed 0.8270 (95% CI, confidence interval, CI 0.8260-0.8280) as area under the receiver operating characteristic curve (AUC) in train cohort, 0.8274 (95% CI 0.8286-0.8298) AUC in validation cohort, and 0.8303 (95% CI 0.8289-0.8316) AUC in test cohort. Then DeepCMM was packaged into a Windows 64-bit software for doctors to use., Conclusion: Deep learning survival model for cutaneous malignant melanoma (DeepCMM) can offer a reliable prediction on cutaneous malignant melanoma patients' overall survival., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Immunohistochemistry-based protein biomarkers can provide useful prognostic information in cutaneous melanoma. The independent prognostic value of Ki-67 has been studied with variable results. PReferentially expressed Antigen in MElanoma (PRAME) immunohistochemistry is a useful new ancillary tool for distinguishing cutaneous nevi from melanoma; however, its prognostic value has not been well studied. We evaluated PRAME as a prognostic marker in cutaneous melanoma, compared to Ki-67., Methods: We analyzed the immunohistochemical expression of PRAME and Ki-67 in 165 melanocytic lesions, including 92 primary melanomas, 19 metastatic melanomas, and 54 melanocytic nevi using tissue microarrays. PRAME immunostaining was scored based on the percentage of positive nuclei: 0 <1%, 1+ 1%-25%, 2+ 26%-50%, 3+ 51%-75%, and 4+ >75%. The percentage of Ki-67-positive tumor nuclei was used to calculate the proliferation index., Results: PRAME and Ki-67 both showed significantly increased expression in melanomas compared to nevi (p < 0.0001 and p < 0.001, respectively). There was no significant difference in PRAME expression in primary versus metastatic melanomas. By contrast, the Ki-67 proliferation index was higher in metastatic melanoma than in primary melanoma (p = 0.013). Increased Ki-67 index correlated with ulceration (p < 0.001), increased Breslow depth (p = 0.001), and higher mitotic rate (p < 0.0001), whereas increased PRAME expression correlated with higher mitotic rate (p = 0.047) and Ki-67 index (p = 0.007). Increased Ki-67 index correlated with worse disease-specific survival in patients with primary melanoma (p < 0.001), but PRAME expression did not show prognostic significance in disease-specific survival (p = 0.63). In a multivariable analysis of patients with primary melanoma, tumor Breslow depth, ulceration, mitotic rate, and Ki-67 index were each independent predictors of disease-specific survival (p = 0.006, 0.02, 0.001, and 0.04, respectively); however, PRAME expression was not predictive of disease-specific survival (p = 0.64)., Conclusion: Ki-67 is an independent prognostic marker; although increased PRAME expression correlates with the Ki-67 proliferation index and mitotic rate, PRAME is not an independent prognostic marker for cutaneous melanoma. PRAME and Ki-67 are useful ancillary tools for distinguishing benign from malignant melanocytic lesions., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background/aim: Cutaneous melanoma, a melanocyte malignancy, can be divided into many clinical subtypes that differ in presentation, demographics, and genetic profile. In this study, we used next-generation sequencing (NGS) analysis to review genetic alterations in 47 primary cutaneous melanomas in the Korean population and compared them to alterations from melanomas in Western populations., Patients and Methods: We retrospectively reviewed clinicopathologic and genetic features of 47 patients diagnosed with cutaneous melanomas between 2019-2021 at Severance Hospital, Yonsei University College of Medicine. NGS analysis was performed at diagnosis to evaluate single nucleotide variations (SNVs), copy number variations (CNVs), and genetic fusions. Genetic features in Western cohorts of melanoma were then compared with previous studies performed in the USA: Cohort 1 (n=556), Cohort 2 (n=79), and Cohort 3 (n=38)., Results: The most common histological classification of melanoma was the acral lentiginous type (23/47, 48.9%). BRAF V600 mutation was most frequent (11/47, 23.4%), but was significantly lower compared to Cohort 1 (240/556, 43.2%) and Cohort 2 (34/79, 43.0%) (p=0.0300). CNV analysis identified amplifications in chromosomes 12q14.1-12q15 (11/47, 23.4%) including CDK4 and MDM2 genes and 11q13.3 (9/47, 19.2%) including CND1, FGF19, FGF3, and FGF4 genes more frequently in the present study population than Cohort 1 (p<0.0001)., Conclusion: These results clearly demonstrated differences in genetic alterations between melanomas in Asian and Western populations. Therefore, BRAF V600 mutation should be considered a significant signaling pathway explaining melanoma pathogenesis occurrence in both Asian and Western populations, whereas loss of chromosome 9p21.3 is unique to melanomas in Western populations., (Copyright © 2023, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: To evaluate the efficiency of a novel lymph node radiotracer 99m Tc-rituximab in sentinel lymph node (SLN) lymphoscintigraphy and SLN biopsy (SLNB), and the influence of SLNB results on the prognosis of cutaneous malignant melanoma (CMM) patients., Methods: A retrospective study was performed on 533 patients with CMM who underwent lymphoscintigraphy and SLNB. All patients received a preoperative peritumoral injection of 11.1-18.5 MBq of 99m Tc-rituximab 0.5 to 1 h before lymphoscintigraphy and SLNB., Results: The detection rate of lymphoscintigraphy and SLNB was both 99.81% (532/533), and the average number of detected SLNs was 2.1 (range 1 to 8) and 2.7 (range 1 to 11) per patient, respectively. 12.1% SLNs and 22.2% patients were found metastatic, with an average of 1.5 (range 1 to 5) metastatic SLNs per patient. The SLN metastatic rates were different in patients with different Breslow thickness, Clark levels, ulceration, mitotic counts, and HMB45 expression (p < 0.05). Ninety patients were proceeded with the regional lymph node dissection (RLND) after SLNB, and the sensitivity, specificity and accuracy of SLNB in metastatic diagnosis is 97.4, 100 and 96.7%, respectively. And SLNs with metastases was an independent prognostic factor for OS and PFS by multivariate prognostic analyses (HR was 5.9 and 4.3, p < 0.001). For patients with metastatic SLNs, the non-SLNs with metastasis and non-SLNs without metastasis in RLND, and observation groups showed different mean PFS as 14.9, 24.8 and 25.5 months (p = 0.018), but no statistically significant difference existed in the OS., Conclusion: The novel radiotracer 99m Tc-rituximab could identify SLNs specifically in SLN lymphoscintigraphy and SLNB in CMM patients, and the pathology obtained from SLNB rather than from RLND better indicated the staging and long-term prognosis., (© 2022. The Author(s) under exclusive licence to The Japanese Society of Nuclear Medicine.)

Malignant melanoma is the most aggressive skin cancer that originates from melanocytes. Primary or metastatic pleural melanoma shares clinical and imaging characteristics with primary pleural tumors, such as pleural mesothelioma. Identification of the primary site can be challenging to distinguish between primary and secondary melanomas. We report a case of a 46-year-old woman with metastatic, rapidly progressing pleural melanoma mimicking primary pleural tumor. The metastatic pleural tumor from a primary cutaneous melanoma was diagnosed by reevaluating a previous surgical specimen. When evaluating patients with pleural melanoma, the primary site should be reevaluated to distinguish between primary and secondary melanomas., (© 2022 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Introduction: The incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. The aim of this study was to evaluate the epidemiology of CMM in Reunion Island, a French overseas department whose population is characterized by high ethnic diversity and high exposure to ultraviolet radiation., Methods: This cross-sectional study examined all cases of in situ CMM and invasive CMM diagnosed between 1 January and 31 December 2015 in the Reunionese population., Results: One hundred and three new cases of CMM were recorded in Reunion Island in 2015: 33 cases of in situ CMM and 70 cases of invasive CMM. The sex ratio of men to women was 1.3 and 80% of patients had a fair skin phototype (Fitzpatrick skin phototype≤III). Age-standardized incidence rates of invasive CMM for all skin phototypes combined were 6.7/100,000 person-years (PY) in women and 5.3/100,000 PY in men. Crude incidence rates of invasive CMM for fair skin phototypes were estimated to be over 21/100,000 PY in women and over 25/100,000 PY in men., Conclusions: In Reunion Island, the incidence of CMM in the population with fair skin phototype is very high. Primary and secondary prevention measures should be reinforced and tailored to the local context., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: The current vitamin D deficiency epidemic is accompanied by an increase in endemic skin cancer. There are still multiple controversies. This review aims to give practical recommendations regarding vitamin D among people at risk or with a personal history of skin cancer., Methods: Narrative review including human research articles published between 2011 and 2021, elaborated bearing in mind an epidemiological, patient-centered approach., Results: Ultraviolet (UV) exposure (neither artificial nor natural) is not the ideal source to synthesize vitamin D. There is conflicting epidemiological evidence regarding vitamin D, non-melanoma skin cancer (NMSC), and cutaneous melanoma (CMM), confounded by the effect of sun exposure and other factors., Conclusions: Current evidence is controversial, and there are no widely applicable strategies. We propose three practical recommendations. Firstly, sun protection recommendations should be kept among people at risk or with a personal history of skin cancer. Secondly, vitamin D should preferably be sourced through diet. In patients with melanoma or at risk of cutaneous cancer, serum vitamin D checks are warranted to detect and avoid its insufficiency.

Cutaneous malignant melanoma (CMM) is responsible for ≥1/2 of skin cancer‑related mortalities. The aberrant expression of long non‑coding RNAs (lncRNAs) has been associated with the development of CMM. However, to the best of our knowledge, the role of the lncRNA TINCR ubiquitin domain containing (TINCR) in CMM has not been previously investigated, and thus, the current study aimed to evaluate this in vitro and in vivo . Reverse transcription‑quantitative PCR (RT‑qPCR) was used to analyze microRNA (miR)‑424‑5p expression, and RT‑qPCR and western blotting were used to measure TINCR, large tumor suppressor kinase 1 (LATS1), cellular communication network factor 2 (CTGF), cellular communication network factor 1 (CCN1) and AXL receptor tyrosine kinase (AXL) mRNA and protein expression levels, respectively. Cell Counting Kit‑8, flow cytometry and Transwell assays were used to detect the proliferation, apoptosis and invasion of CMM cell lines, respectively. The binding sites between TINCR and miR‑424‑5p were predicted using the miRDB database. A dual luciferase reporter assay and RT‑qPCR were used to identify the relationship between TINCR and miR‑424‑5p in CMM cell lines. The bioinformatics analysis revealed that TINCR was one of the most significantly downregulated lncRNAs in CMM, and advanced stage CMM tissues showed the greatest decrease in TINCR expression. Moreover, in the collected CMM tissues and tested cell lines of the current study, TINCR expression was found to be downregulated compared with the respective controls. Notably, TINCR overexpression inhibited the expression levels of CTGF, CCN1 and AXL, decreased the proliferation and invasion, and induced the apoptosis of CMM cell lines. In addition, a mutual binding association was identified between miR‑424‑5p and TINCR in CMM cells. LATS1, a target of miR‑424‑5p, was found to be positively regulated by TINCR. TINCR activated Hippo signaling and repressed the activity of Yes 1 associated transcriptional regulator by regulating LATS1 expression, while LATS1 knockdown reversed the effect of TINCR overexpression on CMM cells. Collectively, the findings of the present study suggested that TINCR may attenuate the progression of CMM by regulating the miR‑424‑5p/LATS1 signaling axis. These results indicated that TINCR may play a tumor suppressive role in CMM.

Background: For patients with sentinel lymph node (SLN)-positive cutaneous melanoma, the Second Multicenter Selective Lymphadenectomy trial demonstrated equivalent disease-specific survival (DSS) with active surveillance using nodal ultrasound versus completion lymph node dissection (CLND). Adoption and outcomes of active surveillance in clinical practice and in adjuvant therapy recipients are unknown., Methods: In a retrospective cohort of SLN-positive adults treated at 21 institutions in Australia, Europe, and the United States from June 2017 to November 2019, the authors evaluated the impact of active surveillance and adjuvant therapy on all-site recurrence-free survival (RFS), isolated nodal RFS, distant metastasis-free survival (DMFS), and DSS using Kaplan-Meier curves and Cox proportional hazard models., Results: Among 6347 SLN biopsies, 1154 (18%) were positive and had initial negative distant staging. In total, 965 patients (84%) received active surveillance, 189 (16%) underwent CLND. Four hundred thirty-nine patients received adjuvant therapy (surveillance, 38%; CLND, 39%), with the majority (83%) receiving anti-PD-1 immunotherapy. After a median follow-up of 11 months, 220 patients developed recurrent disease (surveillance, 19%; CLND, 22%), and 24 died of melanoma (surveillance, 2%; CLND, 4%). Sixty-eight patients had an isolated nodal recurrence (surveillance, 6%; CLND, 4%). In patients who received adjuvant treatment without undergoing prior CLND, all isolated nodal recurrences were resectable. On risk-adjusted multivariable analyses, CLND was associated with improved isolated nodal RFS (hazard ratio [HR], 0.36; 95% CI, 0.15-0.88), but not all-site RFS (HR, 0.68; 95% CI, 0.45-1.02). Adjuvant therapy improved all-site RFS (HR, 0.52; 95% CI, 0.47-0.57). DSS and DMFS did not differ by nodal management or adjuvant treatment., Conclusions: Active surveillance has been adopted for most SLN-positive patients. At initial assessment, real-world outcomes align with randomized trial findings, including in adjuvant therapy recipients., Lay Summary: For patients with melanoma of the skin and microscopic spread to lymph nodes, monitoring with ultrasound is an alternative to surgically removing the remaining lymph nodes. The authors studied adoption and real-world outcomes of ultrasound monitoring in over 1000 patients treated at 21 centers worldwide, finding that most patients now have ultrasounds instead of surgery. Although slightly more patients have cancer return in the lymph nodes with this strategy, typically, it can be removed with delayed surgery. Compared with up-front surgery, ultrasound monitoring results in the same overall risk of melanoma coming back at any location or of dying from melanoma., (© 2021 American Cancer Society.)

In Oceania, North America and north-western Europe, after decades of increase, cutaneous malignant melanoma (CMM) rates began to stabilise or decline before 2000. Anecdotal evidence suggests that the reversal of the incidence trend is extending to southern Europe. To obtain a formal confirmation, this nationwide study from Italy investigated the incidence trends by birth cohort. Twenty-one local cancer registries covering a population of 15 814 455 provided incidence data for primary CMM registered between 1994 and 2013. Trends in age-standardised rates were analysed using joinpoint regression models and age-period-cohort models. Age-standardised incidence showed a consistent increase throughout the period (estimated annual percent change, 3.6 [95% confidence interval, 3.2-4.0] among men and 2.5 [2.0-3.1] among women). This pattern was confirmed by a sensitivity analysis with removal of low-risk populations of southern Italy. The rates, however, showed a stabilisation or a decrease in men and women aged below 35. Using the cohort of 1949-the median cohort with respect to the number of cases for both genders-as a reference, the incidence rate ratio increased for successive cohorts born until 1973 (women) and 1975 (men), and subsequently tended to decline. For the most recent cohorts in both genders, the risk of disease returned to the level of the cohort of 1949. The changes observed in the latest generations can be interpreted as the earliest manifestations of a birth-cohort-dependent incidence decrease. Our study adds to previous data indicating that the reversal of the long-term upward incidence trend of CMM is extending to southern Europe., (© 2020 Union for International Cancer Control.)

Krüppel-like transcription factor 6 (KLF6) is a ubiquitous tumor suppressor gene involved in regulating cell growth, proliferation, differentiation and angiogenesis. The objective of the study was to investigate the clinical and prognostic significance of KLF6 expression in cutaneous malignant melanoma (CMM) patients. A total of CMM 67 patients were enrolled in this study. The specimens were evaluated by immunohistochemistry to detect KLF6. The positive KLF6 expression in CMM tissues was significantly lower than in normal skin tissues (p < 0.01).The presence of KLF6 in CMM was correlated with ulceration (p < 0.01), lymph node metastasis (p < 0.01) and clinical stage (p < 0.01). The overall 5-year survival rate of the 67 patients was 13.4%. The 5-year survival rate of patients with negative KLF6 expression was correlated with KLF6 expression (p < 0.01), ulceration (p < 0.01), lymph node metastasis (p < 0.01), clinical stage (p < 0.01) and operation type (p < 0.01). Ulceration and clinical staging were independent relevant factors. In conclusion, the presence of KLF6 in CMM was correlated with ulceration, lymph node metastasis, clinical stage and poor prognosis.

Introduction: Cutaneous malignant melanoma (CMM) incidence has risen rapidly in the last 50 years. Poor progression and high mortality characterize CMM, making a thorough understanding of progression and associated factors essential for optimizing care., Aims: We assessed the association between the Neutrophil-to-Lymphocyte Ratio (NLR) and mortality in adults with CMM from an entirely mixed-race Hispanic population during 12 consecutive years of extensive follow-up., Material & Methods: We performed a retrospective cohort study in a tertiary hospital in Peru. NLR was categorized with a cutoff value higher or equal than 3. We collected demographic variables, laboratory results and treatments at baseline of follow-up. Cox regression analysis was performed, and we calculated crude and adjusted hazard ratios (HR) and their 95% confidence interval (95%CI)., Results: The analysis was from 615 CMM cases, and there were 378 deaths. Most melanomas (63.6%) were acral lentiginous. The crude analysis showed that high NLR is a risk factor for mortality, HR = 2.52; 95%CI (2.03-3.14). High NRL ratio remains statistically significant after adjusting for confounding variables, aHR = 1.61; 95%CI (1.16-2.24). Other risk factors for mortality were clinical stages III and IV, older than 60 years, females and greater Breslow thickness., Conclusions: We concluded that high NRL ratio is a risk factor for mortality and should be monitored in every patient who is diagnosed with malignant melanoma during their first blood count. It should then be carried out in follow-up controls for patients of clinical stage III and IV only, or in patients who present a relapse., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. In Sweden, over 4600 cases were diagnosed in 2018. The prognosis after radical surgery varies considerably with tumor stage. In recent years, new treatment options have become available for metastatic CMM. Early onset of treatment seems to improve outcome, which suggests that early detection of recurrent disease should be beneficial. Consequently, in several countries imaging is a part of the routine follow-up program after surgery of high risk CMM. However, imaging has drawbacks, including resources required (costs, personnel, equipment) and the radiation exposure. Furthermore, many patients experience anxiety in waiting for the imaging results and investigations of irrelevant findings is another factor that also could cause worry and lead to decreased quality of life. Hence, the impact of imaging in this setting is important to address and no randomized study has previously been conducted. The Swedish national guidelines stipulate follow-up for 3 years by clinical examinations only., Methods: The TRIM study is a prospective randomized multicenter trial evaluating the potential benefit of imaging and blood tests during follow-up after radical surgery for high-risk CMM, compared to clinical examinations only. Primary endpoint is overall survival (OS) at 5 years. Secondary endpoints are survival from diagnosis of relapse and health-related quality of life (HRQoL). Eligible for inclusion are patients radically operated for CMM stage IIB-C or III with sufficient renal function for iv contrast-enhanced CT and who are expected to be fit for treatment in case of recurrence. The planned number of patients is > 1300. Patients are randomized to clinical examinations for 3 years +/- whole-body imaging with CT or FDG-PET/CT and laboratory tests including S100B protein and LDH. This academic study is supported by the Swedish Melanoma Study Group., Discussion: This is the first randomized prospective trial on the potential benefit of imaging as a part of the follow-up scheme after radical surgery for high-risk CMM., Results: The first patient was recruited in June 2017 and as of April 2020, almost 500 patients had been included at 19 centers in Sweden., Trial Registration: ClinicalTrials.gov , NCT03116412 . Registered 17 April 2017, https://clinicaltrials.gov/ct2/show/study/NCT03116412.

Purpose: This study aimed to assess the efficacy of using MR imaging findings for differentiating cutaneous malignant melanoma (cMM) from cutaneous squamous cell carcinoma (cSCC)., Methods: Preoperative MR images of patients with histopathologically proven primary cMM and primary cSCC were retrospectively reviewed and compared between the two pathologies., Results: A total of 16 patients with primary cMM (7 men and 9 women; age range, 45-97 years; median age, 75 years) and 49 with primary cSCC (37 men and 12 women; age range, 46-90 years; median age, 76 years) were enrolled in this study. Intratumoral T1 hyperintensity compared to that of the dermis was more frequently observed in cMM than in cSCC (50 % vs. 4 %; p < 0.01). Superficial depression (51 % vs. 19 %; p < 0.05), superficial irregular margins (55 % vs. 25 %; p <  0.05), and reticular or linear T2 hyperintensity (27 % vs. 0 %; p <  0.05) were more frequently observed in cSCC than in cMM, respectively., Conclusions: cMM predominantly exhibited intratumoral T1 hyperintensity, whereas cSCC predominantly exhibited superficial depression, superficial irregular margins, reticular or linear T2 hyperintensity., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The current research was aimed to explore the effects of Guizhi Fuling Pills on the proliferation, migration and invasion of human cutaneous malignant melanoma cells and its regulation on the molecular axis of LncRNA TPT1-AS1 / miR-671-5p. Human cutaneous malignant melanoma cells A375 were cultured in vitro and randomly divided into Con group, Guizhi Fuling pills-L group, Guizhi Fuling pills-M group, Guizhi Fuling pills-H group, Guizhi Fuling pills-H + pcDNA group, Guizhi Poria pills-H + pcDNA-TPT1-AS1 group. MTT was used to detect cell proliferation. The Transwell cell test was used to detect cell migration and invasion. qRT-PCR was used to detect the expression of TPT1-AS1 and miR-671-5p. The dual-luciferase report experiment verified the targeting relationship of TPT1-AS1, miR-671-5p. Western blot was used to detect the expression of Ki-67, PCNA, MMP-2 and MMP-9. Compared with Con group, Guizhi Fuling Pills could inhibit cell proliferation, migration and invasion (p&lt;0.05), and also inhibit the expression of Ki-67, PCNA, MMP-2, MMP-9, TPT1-AS1 (p&lt;0.05), promote the expression of miR-671-5p (p&lt;0.05)., and the differences between the indexes of Guizhi Fuling Pill-L group, Guizhi Fuling Pill-M group and Guizhi Fuling Pill-H group were statistically significant (p&lt;0.05). The dual-luciferase report experiment confirmed that TPT1-AS1 could target and bind to miR-671-5p and could regulate the expression and activity of miR-671-5p. Overexpression of TPT1-AS1 could reduce the inhibitory effect of Guizhi Fuling Pills on proliferation, migration and invasion of A375 cells. Guizhi Fuling Pill may reduce the proliferation, migration and invasion of human cutaneous malignant melanoma cells by down-regulating the expression of TPT1-AS1 and up-regulating the expression of miR-671-5p.

Background: Previous studies have evaluated associations of XPG rs17655G&gt;C and XPF rs1799801T&gt;C polymorphisms with a risk of cutaneous malignant melanoma (CMM). However, their results thus remained inconsistent or even contradictory. Thus, the aim of this meta-analysis was to evaluate association of XPG rs17655G&gt;C and XPF rs1799801T&gt;C polymorphism with a risk of CMM., Methods: A comprehensive literature search was performed on PubMed, Web of Science, Scopus, SciELO and CNKI databases up to October 15, 2019 to identify relevant studies. Moreover, a case-control study was conducted to evaluate association of XPF rs1799801T&gt;C with CMM risk in the Iranian population. The odds ratio (OR) and 95% confidence interval (CI) values were used to estimate the strength of the associations., Results: Total of 12 studies including 9 studies with 5,362 cases and 7,195 controls on XPG rs17655G&gt;C and 3 studies with 803 CMM cases and 737 controls on XPF rs1799801T&gt;C were selected. Pooled data revealed that XPF rs1799801T&gt;C polymorphism was significantly associated with an increased risk of CMM under the heterozygote model (CT vs. TT: OR = 1.313; 95% CI 1.062-1.624; P = 0.012). However, XPG rs17655G&gt;C polymorphism was not significantly associated with the risk of CMM in the overall population and by ethnicity. The subgroup analysis showed a significant association between XPG rs17655G&gt;C polymorphism and CMM in polymerase chain reaction-based restriction fragments length polymorphism (PCR-RFLP) group of studies., Conclusion: This meta-analysis result revealed that XPF rs1799801T&gt;C polymorphism may be a risk factor for developing of CMM. However, our pooled data inconsistence with the previous meta-analyses revealed that XPG rs17655G&gt;C polymorphism was not associated with the risk of CMM.

Background: Glutathione S-transferase omega 1 (GSTO1), as a member of the glutathione S-transferase (GST) family genes, has been discovered to be up-regulated in several cancer cell lines which exhibited strong aggressiveness. However, the function of GSTO1 on cutaneous malignant melanoma (CMM) has not been illuminated., Methods: Outcome of expression level and prognosis of GSTO1 were obtained from Oncomine and TCGA database. The specific effects of GSTO1 on the characteristics and regulatory mechanism of CMM cells were demonstrated by cell counting kit-8, colony formation, flow cytometry, and transwell assays in vitro. Western blot was employed to analyze the expression of proliferating cell nuclear antigen (PCNA), p53 and epithelial-to-mesenchymal (EMT) related proteins., Results: We observed that GSTO1 was up-regulated in CMM samples when compared with the corresponding controls. Moreover, patients in CMM with high expression of GSTO1 were more likely to have a poor prognosis. Through in vitro experiments, silenced GSTO1 resulted in inhibition of CMM cells growth and aggressiveness, increased cell apoptosis, and blocked cell cycle. Finally, the expression of PCNA, p53 and EMT-related proteins were changed due to reduction of GSTO1., Conclusions: To sum up, our outcomes exhibited that weakening GSTO1 reduced the proliferation and mobility of CMM cells, increased the apoptosis ability of CMM cells, and arrested cell cycle at G1 phase, which can be achieved by affecting the expression of PCNA, p53 and the EMT process. This discovery provided a new perspective for elucidating the mechanism of CMM, and offered theoretical support for searching clinical therapeutic targets in the future., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Purpose: The aim was to study the mechanism of LncRNA FOXD3-AS1 in cutaneous melanoma., Methods: FOXD3-AS1 levels in 47 pairs of melanoma samples were detected. We used qRT-PCR to detect FOXD3-AS1, miR-325 and MAP3K2 expression in different staging samples and cutaneous melanoma cell lines. We used Kaplan-Meier curve to analyze survival rate in patients with FOXD3-AS1 high and low expression. Sh-FOXD3-AS1, miR-325, miR-325 inhibitor and oeMAP3K2 were transfected. The proliferation of A375 and SK-MEL-1 was detected by CCK8 and EdU labeling assay and cell clone formation assay. Dual luciferase reporter assay and pull down assay was used to confirm the binding site of FOXD3-AS1, miR-325 and MAP3K2. Flow cytometry was applied to detect the effect of lncRNA on cell cycle. The migration and invasion ability were detected by transwell assay., Results: LncRNA FOXD3-AS1 highly expressed in cutaneous melanoma cells and tissues. Patients with highly expressed LncRNA FOXD3-AS1 were always with shorter overall survival time. When LncRNA FOXD3-AS1 was knockdown, proliferation, invasion and migration of cutaneous malignant melanoma, and tumor weight was inhibited, and cell cycle was arrested. LncRNA FOXD3-AS1 negatively regulated the expression of miR-325, and then improved the level of MAP3K2. MiR-325 was with similarly effects on above biological process, and MAP3K2 overexpression could rescue the influence of sh-FOXD3-AS1. Tumor volume and weight were measured to confirm the effect of sh-FOXD3-AS1 in vivo., Conclusion: LncRNA FOXD3-AS1 could promote proliferation, invasion and migration of cutaneous malignant melanoma via regulating miR-325/MAP3K2 axis., (Copyright © 2019 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Early smallpox and Bacillus Calmette-Guérin (BCG) vaccinations have been associated with reduced risk of cutaneous malignant melanoma (CMM). We assessed the association between pre-school smallpox vaccination and early-school BCG vaccination and CMM in a young Danish population., Methods: We conducted a register-based case-cohort study of individuals growing up during the phase-out period of smallpox and BCG vaccination in Denmark (born 1965-1976) utilising the decrease in vaccination during this period. Information on childhood vaccinations and potential confounders from Copenhagen school health records were linked with nationwide registers on cancer (CMM diagnoses), migrations and deaths by personal identification numbers., Results: The individuals were followed from age 18 until 31/12/2014 (maximum age at end of follow-up, 49 years). 188 cases of CMM occurred in the background population of 46,239 individuals; 172 CMM cases (91%) had full information and were analysed. The adjusted hazard ratio (HR) for CMM by BCG and/or smallpox vaccination compared with neither vaccine was 1.29 (95% confidence interval (CI) 0.72-2.31). For smallpox vaccination only, HR = 1.23 (95% CI 0.53-2.86) for BCG vaccination only, HR = 1.13 (95% CI 0.61-2.09) and for both smallpox and BCG vaccination, HR = 1.75 (95% CI 0.87-3.48) compared with none of these. Vaccination below the age of one year gave similar results., Conclusions: We found no strong beneficial effect of smallpox and BCG vaccination against CMM among young adult Danes and with broad confidence intervals our data alone could be compatible with both modest preventive effects, no effects, and modest harmful effects. Our estimates do not contradict a potential modest beneficial effect of neonatal vaccination., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: We recently reported a steady increase in the incidence and mortality of cutaneous malignant melanoma (CMM) in Canada during 1992-2010., Objectives: The objective of this article is to examine the distribution of Canadian CMM patients at the level of provinces, cities, and forward sortation area (FSA) postal codes., Methods: Using 3 Canadian population-based registries, we conducted an in-depth examination of the incidence and mortality trends for 72 565 Canadian CMM patients over the period 1992-2010., Results: We found that among 20- to 39-year-olds, the incidence of CMM in women (7.17 per 100 000 individuals) was significantly higher than in men (4.60 per 100 000 individuals per year). Women age 80 years and older had an incidence of CMM (58.46 cases per 100 000 women per year) more than 4 times greater than the national average (12.29 cases per 100 000 population per year) and a corresponding high mortality rate (20.18 deaths per 100 000 women per year), when compared with the Canadian melanoma mortality of 2.4 deaths per 100 000 per year. In other age groups men had higher incidence and corresponding melanoma mortality rates. We also studied CMM incidence by province, city, and FSA postal codes and identified several high-incidence communities that were located near the coast/waterfronts. In addition, plotting latitude measures for cities and FSAs vs CMM incidence rate confirmed the inverse relationship between geographical latitude and incidence of melanoma in Canada (slope = -0.22 ± 0.05)., Conclusions: This research may help develop sex-, age- and geographic region-specific recommendations to decrease the future burden of CMM in Canada.

Cutaneous malignant melanoma (CMM) ranks the most lethal skin cancer worldwide. However, other risk factors have been hardly explored, aside from ultraviolet radiation (UVR). Polychlorinated biphenyls (PCBs) were implied to be potential risk factors for CMM, although all the evidence was obtained from the western countries. This study examined the relationships between plasma levels of PCBs and CMM risk adjusting for sun sensitivity and sun exposure in a Chinese population, using a case-control study, including 450 CMM cases and 500 healthy controls. Plasma levels of a total of 33 PCB congeners were assayed in both cases and controls. Our results showed that there was a significant association between total summed PCB level and CMM risk, with a 1.44-fold increased risk for those in the highest quartile compared to those in the lowest quartile (OR = 1.44, 95% CI: 1.02-2.03, P for trend = 0.031). Significantly increased ORs were also observed for individual PCB congeners (PCB52, PCB170 and PCB180). These associations persisted after control for sun sensitivity and sun exposure. Our study represents the first evidence conducted in Asians, and does support the hypothesis that PCB exposure increases CMM risk., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The incidence of cutaneous malignant melanoma (CMM) is on the rise in many parts of the world. However, there is limited knowledge on the epidemiology of CMM in Canada., Objective: To conduct a comprehensive population-based study of CMM in Canada., Methods: We examined patient clinical and pathologic characteristics as well as the incidence and mortality trends of CMM in Canada using 3 independent population-based registries., Results: In total, 72,565 Canadian patients were given CMM diagnoses during 1992-2010; 47.5% were women. Average age at the time of diagnosis was 56.5 years for women and 60.4 years for men. We report a steady increase in CMM incidence and mortality rates in both sexes. The overall incidence rate of CMM in Canada was 12.29 cases/100,000 person-years. We also report important differences in the incidence and mortality rates between Canadian provinces and territories; the highest incidence of this cancer was documented in Nova Scotia and Prince Edward Island., Limitations: Data on race, clinical disease stage, and Breslow depth of CMM was not available., Conclusion: This study, for the first time, defines the disease burden of CMM in Canada and highlights important longitudinal, geographic, and spatial differences in the distribution of CMM in this country., (Copyright © 2018 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background/objectives: Sunlight is a major risk factor for cutaneous melanoma. However, its interaction with melanoma is complex. In particular, vitamin D is a UVB-derived hormone that has been shown to have anti-cancer effects. In this retrospective pilot study we sought to determine an association between the clinicopathological features of melanoma and the patients' corresponding serum vitamin D level., Methods: In total, 109 primary melanomas diagnosed between 2001 and 2013 were retrospectively identified from our institutional database with a corresponding 25-hydroxyvitamin D3 level estimated within 6 months of diagnosis. Tumour, clinical (age, sex, tumour location) and pathological (thickness, mitosis, ulceration, Clark level, subtype, metastatic status) parameters were correlated with vitamin D. For statistical analysis, an unpaired Student's t-test and anova was used for categorical variables, and Spearman's correlation for continuous variables., Results: Vitamin D level was inversely associated with Breslow thickness as a dichotomous, categorical and continuous variable. The association remained significant when controlled for patient's age and sex (P = 0.026). Vitamin D was higher in non-ulcerated tumours compared with ulcerated tumours (P = 0.006) and in tumours with mitotic rate <1/mm 2 compared with ≥1/mm 2 (P = 0.036). A significant association was found between vitamin D level and tumour histological subtype (P = 0.019). On subgroup analysis, significant associations were found between superficial spreading melanoma (SSM) and nodular melanoma (P = 0.026), and SSM and acral lentiginous melanoma (P = 0.007)., Conclusion: A high vitamin D status may benefit prognosis in patients diagnosed with primary melanoma. A prospective cohort analysis with a large sample and controlled for other vitamin D confounders would validate these findings., (© 2017 The Australasian College of Dermatologists.)

Aims: MicroRNA-186 (miR-186) has been shown to be involved in various types of cancer. The purpose of this study was to investigate the expression level and functional role of miR-186 in human cutaneous malignant melanoma cells., Subjects and Methods: Expression of miR-186 was analyzed in human cutaneous malignant melanoma (CMM) cell lines SK-MEL-1, G-361, A375 and A875, and human normal epidermal melanocytes cell line HEMn-LP by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Additionally, the functional role of miR-186 on melanoma cells was investigated by transfection of miR-186 mimic followed by analyses of cell proliferation, apoptosis, and metastasis., Results: We found that the expression levels of miR-186 were decreased in CMM cell lines compared with normal epidermal melanocytes cell line. Moreover, overexpression of miR-186 inhibited cells proliferation through abrogating the G 1 -S transition, and reduced cells migration and invasion., Conclusions: Our findings suggested that miR-186 exhibit an inhibitory effect on CMM cell proliferation, migration, and invasion; thus, may serve as a potential therapeutic target for human CMM intervention., Competing Interests: There are no conflicts of interest

Outcome data comparing patients with multiple primary invasive cutaneous malignant melanomas (MPMs) to single primary invasive cutaneous malignant melanomas (SPMs) show conflicting results. We have analyzed differences in disease-specific survival between these patients in a nationwide population-based setting. From the Swedish Melanoma Register, 27,235 patients were identified with a first invasive cutaneous malignant melanoma (CMM) between 1990 and 2007, followed-up through 2013. Of these, 700 patients developed MPMs. Cox proportional hazard regression was used for adjusted cause-specific hazard ratios (HRs). An interval of ≤5 years between CMM diagnoses was significantly correlated to a decreased CMM-specific survival in Stage I-II MPM- vs. SPM-patients (HR 1.32; 95% CI 1.04-1.67; p = 0.02). MPM-patients with longer time interval between diagnoses experienced similar risk of CMM-death as SPM-patients. The risk of CMM-death increased by almost 50% above the expected outcome according to stage of the index CMM by the diagnosis of a second CMM (HR 1.48; 95% CI 1.19-1.85; p < 0.001). MPM vs. SPM-patients had a worse outcome (HR 1.38; 95% CI 1.05-1.83; p = 0.001). This emphasizes the importance of prevention efforts in SPM-patients to decrease the risk of subsequent CMMs and has implications for more vigilant follow-up in MPM-patients., (© 2017 UICC.)

Background: For malignant melanoma, other risk factors aside from sun exposure have been hardly explored. Polychlorinated biphenyls (PCBs)-mainly from fatty fish- may affect melanogenesis and promote melanoma progression, while long-chain n-3 polyunsaturated fatty acids seem to exert antineoplastic actions in melanoma cells., Objectives: We aimed to assess the association of validated estimates of dietary PCB exposure as well as the intake of eicosapentaenoic acid and docosahexaenoic acid (EPA-DHA), accounting for sun habits and skin type, with the risk of malignant melanoma in middle-aged and elderly women., Methods: We included 20,785 women at baseline in 2009 from the prospective population-based Swedish Mammography Cohort. Validated estimates of dietary PCB exposure and EPA-DHA intake were obtained via a food frequency questionnaire. Incident melanoma cases were ascertained through register-linkage., Results: During 4.5 years of follow-up, we ascertained 67 incident cases of melanoma. After multivariable adjustments, exposure to dietary PCBs was associated with four-fold increased risk of malignant melanoma (hazard ratio [HR], 4.0 [95% confidence interval {CI}, 1.2-13; P for trend = 0.02]), while EPA-DHA intake was associated with 80% lower risk (HR, 0.2 [95% CI, 0.1-0.8; P for trend = 0.03]), comparing the highest exposure tertiles with the lowest., Conclusion: While we found a direct association between dietary PCB exposure and risk of melanoma, EPA-DHA intake showed to have a substantial protective association. Question of benefits and risk from fish consumption is very relevant and further prospective studies in the general population verifying these findings are warranted., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

A shared genetic susceptibility between cutaneous malignant melanoma (CMM) and Parkinson's disease (PD) has been suggested. We investigated this by assessing the contribution of rare variants in genes involved in CMM to PD risk. We studied rare variation across 29 CMM risk genes using high-quality genotype data in 6875 PD cases and 6065 controls and sought to replicate findings using whole-exome sequencing data from a second independent cohort totaling 1255 PD cases and 473 controls. No statistically significant enrichment of rare variants across all genes, per gene, or for any individual variant was detected in either cohort. There were nonsignificant trends toward different carrier frequencies between PD cases and controls, under different inheritance models, in the following CMM risk genes: BAP1, DCC, ERBB4, KIT, MAPK2, MITF, PTEN, and TP53. The very rare TYR p.V275F variant, which is a pathogenic allele for recessive albinism, was more common in PD cases than controls in 3 independent cohorts. Tyrosinase, encoded by TYR, is the rate-limiting enzyme for the production of neuromelanin, and has a role in the production of dopamine. These results suggest a possible role for another gene in the dopamine-biosynthetic pathway in susceptibility to neurodegenerative Parkinsonism, but further studies in larger PD cohorts are needed to accurately determine the role of these genes/variants in disease pathogenesis., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Increasing evidence has suggested that miR-330-5p can function as a tumor suppressor in different types of cancers. However, the effects and underlying mechanisms of miR-330-5p in the development of cutaneous malignant melanoma (CMM) remain largely unknown. The aim of the present study was to investigate the role of miR-330-5p in CMM and to determine the molecular mechanisms underlying its action., Materials and Methods: The expression level of miR-330-5p was detected in 26 cases of primary CMM tissues and cell lines by real-time quantitative polymerase chain reaction. We also assessed whether overexpression of miR-330-5p influences in vitro cell proliferation, invasion, and migration. Western blotting analysis was used to detect the influence of miR-330-5p on the targets, and Pearson analysis was used to calculate the correlation between the expression of targets gene and miR-330-5p in CMM tissues., Results: Our study showed that miR-330-5p was downregulated in CMM tissues (P = 0.010) and cell lines (P < 0.05), and patients with high mitotic activity showed lower miR-330-5p expression levels (P = 0.002). Enforced expression of miR-330-5p inhibits malignant CMM cells proliferation and migration and led to downregulation of the TYR and PDIA3 protein. Moreover, the expression level of miR-330-5p in CMM tissues showed inverse relationship with the expression level of TYR and PDIA3 protein., Conclusions: In conclusion, our findings suggested that miR-330-5p represents a potential tumor-suppressive miRNA and plays an important role in CMM progression by suppressing TYR and PDIA3 expression., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Melanoma is one of the most aggressive types of skin cancer. The purpose of this study was to evaluate the use of two biomarkers, ProEx C and glucose transporter isoform 1 (GLUT1), in the diagnosis and prognostication of melanoma., Materials and Methods: We analyzed 129 melanomas and 59 benign nevi in a tissue microarray using immunohistochemical method with antibodies to topoisomerase IIα (TOP2A) and minichromosome maintenance complex component 2 (MCM2) using ProEx C and to GLUT1., Results: The average proliferative index by ProEx C immunostain was significantly higher in melanomas (37.5%) compared to benign nevi (1.9%) as was the expression of GLUT1 (p<0.0001 respectively). Dermal mitosis was found to correlate positively with both ProEx C and GLUT1 (p=0.003 and p<0.001, respectively). Ulceration and tumor thickness positively correlated with GLUT1 expression (p=0.013 and p=0.033, respectively), but not with ProEx C staining. There was a significant association between increasing ProEx C index and stronger expression of GLUT1 (p<0.001). Kaplan-Meier disease-specific survival analyses indicated that patients whose melanoma exhibited expression of GLUT1 had a significantly lower rate of disease-specific survival than patients whose melanoma did not (p=0.039). However, staining by ProEx C did not show a prognostic significance in disease-specific survival., Conclusion: ProEx C and GLUT1 are potentially useful markers in differentiation of melanoma from nevi. Absence of GLUT1 expression in patients with primary melanoma predicts better survival., (Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Cutaneous malignant melanoma (CMM) is an epidemic cancer in the United States. Survival rates for invasive CMM have not increased in past decades despite numerous clinical trials and the effective use of various combinations of chemotherapy agents to treat other cancers. Recent research has investigated the role of melanocortin 1 receptor (MC1R), a gene associated with red-hair phenotype in White individuals and with increased risk for developing CMM, in the mitogen-activated protein kinase (MAPK) pathway. This limited narrative review discusses the incidence, history, and risk factors for CMM. It explores familial CMM and provides a brief review of melanocyte development and melanogenesis. Histology of CMM and cytogenetic techniques used to identify CMM mutations is also discussed. The structure and function of MC1R is described, with particular attention to MC1R's role in the MAPK pathway. Finally, the review touches on individualized therapy for CMM using genetic biomarkers and explores the promise of genomic research for finding effective treatments., (© The Author(s) 2014.)

The relationship of ovostatin 2 (OVOS2) expression with the clinicopathological features of cutaneous malignant melanoma (CMM) was investigated to identify OVOS2 expression in cutaneous melanocytic lesions, and to reveal whether OVOS2 has a function in melanoma progression. Eight specimens of CMM and paracancerous tissue were analyzed using real-time polymerase chain reaction (PCR) and western blot for the mRNA and protein expression of OVOS2, respectively. Immunohistochemical staining was performed on 52 CMM and 62 nevi, followed by clinicopathological significance analysis. The proliferative cells were visualized by staining with Ki-67 antibody. The intensity of angiogenesis was assessed by staining with vascular endothelial growth factor (VEGF). Real-time PCR and western blot analyses showed that OVOS2 was significantly upregulated in cutaneous melanoma than in paired normal skins. Immunohistochemistry showed that 86.5% (45/52) of malignant cases showed OVOS2 cytoplasmic expression compared with 29% (18/62) in benign nevi. OVOS2 expression was significantly higher in invasive and metastatic melanoma than in in situ melanoma (P < 0.01). Furthermore, OVOS2 expression was positively correlated with the known prognostic variables of melanoma including clinical stage, Clark level and Breslow depth. It was also significantly associated with ulcer status, Ki-67 labeling index and VEGF expression in primary melanoma. OVOS2 expression was significantly increased in CMM, which increased incrementally from benign nevi to melanoma and appeared to be involved in the progression of melanoma., (© 2013 Japanese Dermatological Association.)

Aims: The incidence rates of cutaneous malignant melanoma (CMM) increase throughout the world, in spite of introduction of strategies for prevention. However, a decrease in incidence rates is observed in some countries. If the reason for this could be found, it might be useful to transfer the knowledge to other fields of medicine., Methods: CMM age-standardized incidence rates in different age groups in Norway were obtained from NORDCAN for the years 1970-1989 and 1990-2009., Results: Until 1990, the CMM rates increased, but after that time a stabilization or a decrease was observed for young age groups (15-54 years old), while in older generations (>55 years old) the rates continued to increase., Conclusions: The decreasing CMM pattern in young age groups may be due to changing patterns to sunlight in sunbathing and use of sunbeds.