Melanoma
Support for the Safe Use of Zinc Oxide Nanoparticle Sunscreens: Lack of Skin Penetration or Cellular Toxicity after Repeated Application in Volunteers
Zinc oxide is a widely used broad-spectrum sunscreen, but concerns have been raised about the safety of its nanoparticle (NP) form. We studied the safety of repeated application of agglomerated zinc oxide (ZnO) NPs applied to human volunteers over 5 days by assessing the skin penetration of intact ZnO-NPs and zinc ions and measuring local skin toxicity. Multiphoton tomography with fluorescence lifetime imaging microscopy was used to directly visualize ZnO-NP skin penetration and viable epidermal metabolic changes in human volunteers.Assessing the Incremental Contribution of Common Genomic Variants to Melanoma Risk Prediction in Two Population-Based Studies
It is unclear to what degree genomic and traditional (phenotypic and environmental) risk factors overlap in their prediction of melanoma risk. We evaluated the incremental contribution of common genomic variants (in pigmentation, nevus, and other pathways) and their overlap with traditional risk factors, using data from two population-based case-control studies from Australia (n = 1,035) and the United Kingdom (n = 1,460) that used the same questionnaires. Polygenic risk scores were derived from 21 gene regions associated with melanoma and odds ratios from published meta-analyses.Fractional Sunburn Threshold UVR Doses Generate Equivalent Vitamin D and DNA Damage in Skin Types I–VI but with Epidermal DNA Damage Gradient Correlated to Skin Darkness
Public health guidance recommends limiting sun exposure to sub-sunburn levels, but it is unknown whether these can gain vitamin D (for musculoskeletal health) while avoiding epidermal DNA damage (initiates skin cancer). Well-characterized healthy humans of all skin types (I–VI, lightest to darkest skin) were exposed to a low-dose series of solar simulated UVR of 20%–80% their individual sunburn threshold dose (minimal erythema dose). Significant UVR dose responses were seen for serum 25-hydroxyvitamin D and whole epidermal cyclobutane pyrimidine dimers (CPDs), with as little as 0.2 minimal erythema dose concurrently producing 25-hydroxyvitamin D and CPD.Continued Increase in Melanoma Incidence across all Socioeconomic Status Groups in California, 1998–2012
Melanoma incidence has been increasing in light-skinned populations worldwide, but the reasons for the increase have been controversial. Our prior assessment in California non-Hispanic whites showed substantial increases in invasive melanoma incidence for tumors of all thicknesses in all neighborhoods categorized by socioeconomic status (SES) between 1988–1992 and 1998–2002. To understand whether these trends continued, we updated our assessment to include the diagnosis period 2008–2012 and more accurate pathologic stage at diagnosis.Survival of Patients with Cutaneous Squamous Cell Carcinoma: Results of a Prospective Cohort Study
Cutaneous squamous cell carcinoma (cSCC) is an increasing health burden in white populations. We prospectively assessed risk factors for tumor-specific and overall survival in 1,434 patients who underwent surgery for cSCC between January 24, 2005, and May 29, 2015. A total of 2,149 invasive cSCCs were analyzed. Univariate and multivariate survival analyses included tumor thickness, horizontal size, body site, histological differentiation, desmoplastic growth, history of multiple cSCCs, and immunosuppression.Serial or Parallel Metastasis of Cutaneous Melanoma? A Study of the German Central Malignant Melanoma Registry
For more than a century the Halstedian hypothesis of contiguous metastasis from the primary tumor through the lymphatics to distant sites shaped lymph node surgery for melanoma. We challenge this dogma of serial metastatic dissemination. A single-center series of 2,299 patients with cutaneous metastatic melanoma was investigated to analyze overall survival and distant metastasis-free survival of stage IV patients with or without primary lymphatic metastasis. Results were then compared with those of 2,134 patients from three independent centers of the German Central Malignant Melanoma Registry.Incidence, Mortality, and Trends of Nonmelanoma Skin Cancer in Germany
Increasing incidence rates (IRs) of nonmelanoma skin cancer (NMSC) in white populations have been described worldwide. Cancer registry data from the Saarland and Schleswig-Holstein federal states were used to analyze incidence and mortality trends in Germany. Age-standardized rates were compared with crude rates to assess disease burden. Joinpoint regression models were used to estimate annual percentage changes and 95% confidence intervals, allowing us to assess temporal trends between 1970 and 2012.Association between Body Mass Index, C-Reactive Protein Levels, and Melanoma Patient Outcomes
Obesity is a known risk factor for cancer development (Arnold et al., 2016; Basen-Engquist and Chang, 2011; Renehan et al., 2015) and death (Calle et al., 2003). Obesity has been associated with an increased risk of developing melanoma in men (Sergentanis et al., 2013) and with thicker primary melanomas (Skowron et al., 2015). The inflammatory adipokine leptin promotes melanoma progression in mice (Amjadi et al., 2011; Brandon et al., 2009; Gogas et al., 2008); elevated leptin levels may predict melanoma sentinel node metastasis (Oba et al., 2016).Cigarette Smoking and the Risks of Basal Cell Carcinoma and Squamous Cell Carcinoma
Sunlight is the principal environmental risk factor for keratinocyte cancers, but other carcinogens have also been implicated, including tobacco smoke. Findings have been conflicting, however. We investigated associations between cigarette smoking and incidence of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) in QSkin, a prospective study of skin cancer (N = 43,794). Smoking history was self-reported at baseline; newly diagnosed BCCs and SCCs were ascertained through data linkage and verified by histopathology reports.Surgery Versus 5% Imiquimod for Nodular and Superficial Basal Cell Carcinoma: 5-Year Results of the SINS Randomized Controlled Trial
We previously reported modest clinical 3-year benefit for topical imiquimod compared with surgery for superficial or nodular basal cell carcinoma at low-risk sites in our noninferiority randomized controlled SINS trial. Here we report 5-year data. Participants were randomized to imiquimod 5% cream once daily (superficial basal cell carcinoma, 6 weeks; nodular basal cell carcinoma, 12 weeks) or excisional surgery (4-mm margin). The primary outcome was clinical absence of initial failure or signs of recurrence at the 3-year dermatology review.Epidemiology of Lentigo Maligna and Lentigo Maligna Melanoma in the Netherlands, 1989–2013
Lentigo maligna (LM) is considered a precursor to LM melanoma (LMM). We assessed trends in LM and LMM incidence rates between 1989 and 2013 in the Netherlands, and estimated the risk of an LMM after LM. Data on newly diagnosed LM and LMM were obtained from the Netherlands Cancer Registry and PALGA: Dutch Pathology Registry. Age-standardized incidence rates (European standardized rate), estimated annual percentage changes, and the cumulative incidence of LMM after LM were calculated. Between 1989 and 2013, 10,545 patients were diagnosed with a primary LM and 2,898 with a primary LMM in the Netherlands.Ten-Year Survival after Multiple Invasive Melanomas Is Worse than after a Single Melanoma: a Population-Based Study
The prognosis of melanoma patients who are diagnosed with multiple primary lesions remains controversial. We used a large population-based cohort to re-examine this issue, applying a delayed entry methodology to avoid survival bias. Of 32,238 eligible patients diagnosed between 1995 and 2008, 29,908 (93%) had a single invasive melanoma, 2,075 (6%) had two, and 255 (1%) had three. Allowing for differences in entry time, 10-year cause-specific survival for these three groups was 89% (95% confidence interval [CI] = 88–90%), 83% (95% CI = 80–86%), and 67% (95% CI = 54–81%), respectively.Promoter Methylation of PTEN Is a Significant Prognostic Factor in Melanoma Survival
Structural compromise of the tumor suppressor gene, phosphatase and tensin homolog (PTEN), occurs in 10% of melanoma specimens, and loss of PTEN expression through DNA methylation of the PTEN promoter region has also been reported in a number of other malignancies. However, the role of PTEN promoter methylation in melanoma is not well understood. We thus sought to elucidate the prevalence of PTEN promoter methylation in melanoma specimens, its relationship to clinical features, and its impact on the outcome of patients with melanoma.Serum miR-16: A Potential Biomarker for Predicting Melanoma Prognosis
Melanoma is among the most malignant cancers with notorious aggressiveness, and its prognosis is greatly influenced by progression status. Serum microRNAs are small noncoding RNAs with high stability and easy accessibility in human blood. Their expression profiles are frequently dysregulated in cancers; hence, levels of serum microRNAs may reflect progression status and thus predict melanoma prognosis. In a hospital based case-control study, we found a significant reduction of serum miR-16 level in melanoma patients compared with cancer-free controls (P < 0.001).Development and Validation of the Vitiligo Extent Score (VES): an International Collaborative Initiative
The clinical assessment of vitiligo involves an estimation of the affected body surface area. The most commonly used method is the “palm of hand 1% rule” as integrated in the Vitiligo Area Scoring Index. However, this method can be challenging and time consuming. In this study, we introduce a global Vitiligo Extent Score (VES). In the first part of the study, this measurement instrument was developed and subsequently optimized during a pilot scoring session. In a subsequent stage, the inter- and intrarater reliability of the instrument were tested.Histologic and Phenotypic Factors and MC1R Status Associated with BRAFV600E, BRAFV600K, and NRAS Mutations in a Community-Based Sample of 414 Cutaneous Melanomas
Cutaneous melanomas arise through causal pathways involving interplay between exposure to UV radiation and host factors, resulting in characteristic patterns of driver mutations in BRAF, NRAS, and other genes. To gain clearer insights into the factors contributing to somatic mutation genotypes in melanoma, we collected clinical and epidemiologic data, performed skin examinations, and collected saliva and tumor samples from a community-based series of 414 patients aged 18 to 79, newly diagnosed with cutaneous melanoma.
