MMP19 is upregulated during melanoma progression and increases invasion of melanoma cells

During the progression of cutaneous melanomas, matrix metalloproteinases (MMPs) facilitate the tumour cells to traverse the basement membrane and invade the dermis. In this study, we analysed the expression of MMP19 in the course of melanoma progression. Although MMP19 was absent in melanocytes and melanoma cells of early stages of melanoma development, its expression was strongly upregulated in the neighbouring keratinocytes that may facilitate the vertical outgrowth of melanoma cells. In contrast to early stages, MMP19 was upregulated during the vertical growth phase of melanoma and in metastases. The upregulation of MMP19 in melanoma of Clark levels IV and V correlates with that of MMP2 and also simultaneously with ceased expression of E-cadherin. To reveal whether MMP19 facilitates the invasion of melanomas, we examined adhesion and migratory capacity of selected melanoma cell lines. Melanoma cell lines with low expression of MMP19 exhibited increased adhesion to various substrates and lower migration in comparison with the cell line with higher expression of MMP19. Moreover, ectopic expression of MMP19 could restore the migratory capacity of melanoma cells with low endogenous level of MMP19. These results suggest that the increase of MMP19 expression hallmarks the progression of cutaneous melanoma and might augment melanoma growth by promoting the invasion of tumour cells.

Expression and functional significance of VE-cadherin in aggressive human melanoma cells: Role in vasculogenic mimicry

We recently have introduced the term vasculogenic mimicry to describe the unique ability of aggressive melanoma tumor cells to form tubular structures and patterned networks in three-dimensional culture, which “mimics” embryonic vasculogenic networks formed by differentiating endothelial cells. In the current study, we address the biological significance of several endothelial-associated molecules (revealed by microarray analysis) with respect to expression and function in highly aggressive and poorly aggressive human cutaneous melanoma cell lines (established from the same patient). In a comparative analysis, CD31 was not expressed by any of the melanoma cell lines, whereas TIE-1 (tyrosine kinase with Ig and epidermal growth factor homology domains-1) was strongly expressed in the highly aggressive tumor cells with a low level of expression in one of the poorly aggressive cell lines. Vascular endothelial (VE)-cadherin was exclusively expressed by highly aggressive melanoma cells and was undetectable in the poorly aggressive tumor cells, suggesting the possibility of a vasculogenic switch. Down-regulation of VE-cadherin expression in the aggressive melanoma cells abrogated their ability to form vasculogenic networks and directly tested the hypothesis that VE-cadherin is critical in melanoma vasculogenic mimicry. These results highlight the plasticity of aggressive melanoma cells and call into question their possible genetic reversion to an embryonic phenotype. This finding could pose a significant clinical challenge in targeting tumor cells that may masquerade as circulating endothelial cells or other embryonic-like stem cells.

Análise da expressão da proteína NY-ESO-1 no melanoma cutâneo

INTRODUÇÃO: o câncer é a doença que mais mata pessoas com idade abaixo de 85 anos e é um problema de saúde pública. Os tumores podem expressar em determinada fase de seu desenvolvimento proteínas anômalas que podem ser alvo de métodos diagnósticos e de intervenções terapêuticas. A expressão de NY-ESO-1 é detectada em 20 a 40% dos melanomas. Há evidências que esta expressão é mais freqüente em tumores de estágios mais avançados e está associada a um pior prognóstico. OBJETIVOS: determinar a frequência de expressão da proteína NY-ESO-1 no melanoma cutâneo e tentar correlacioná-la com o índice de Breslow, aspectos histopatológicos do melanoma, incluindo o infiltrado linfocítico tumoral, e a morbi-mortalidade dos pacientes. MÉTODOS: o presente estudo é longitudinal de coorte retrospectiva e foi realizado de agosto de 2009 a outubro de 2015. Foram selecionados 89 melanomas de 87 pacientes do Ambulatório de Tumores do Departamento de Dermatologia da FMUSP, divididos em 3 grupos, sendo: grupo 1: 34 melanomas com índice de Breslow <= 1,0 mm; grupo 2: 29 melanomas com índice de Breslow entre 1,1 - 4,0 mm e grupo 3: 26 melanomas com índice de Breslow >= 4,0 mm. As lâminas dos exames anátomo-patológicos destes pacientes foram revisadas quanto ao diagnóstico de melanoma, seu índice de Breslow e a presença de infiltrado linfocítico tumoral. A seguir, realizou-se exame de imunohistoquímica para a determinação da presença do antígeno NY-ESO-1 em todos os 89 tumores coletados e em mais 20 nevos (11 displásicos e 9 intradérmicos) escolhidos ao acaso. Através da revisão dos dados do prontuário, foram obtidos os dados clínicos de: idade, sexo, raça, fototipo da pele, local de aparecimento do melanoma, status do linfonodo sentinela quando realizado, desenvolvimento de metástases e sobrevida dos pacientes. Os dados anátomo-patológicos do tumor analisados foram: tipo histológico, presença de ulceração, e tipo de infiltrado linfocítico tumoral. Nos melanomas que apresentavam infiltrado linfocítico tumoral, foram realizados testes imunohistoquímicos para pesquisa de células CD3+, CD8+, FoxP3+ e CD8+FoxP3+ (duplamente positivas). RESULTADOS: O antígeno NY-ESO-1 esteve presente em 19% dos melanomas cutâneos primários e não foi detectado em nenhum dos 20 nevos pesquisados. A expressão do antígeno NY-ESO-1 esteve estatisticamente relacionada a tumores com espessuras maiores. Apresentou também uma associação inversa com o tipo extensivo superficial em relação aos outros tipos histológicos. O infiltrado linfocítico tumoral dos melanomas NY-ESO-1 positivos continha menor número de células CD3+, que se encontravam isoladas ou arranjadas em pequenos grupos de até 5 células, o que contrastava significantemente com os tumores NY-ESO-1 negativos, com maior densidade de células CD3+, dispostas em grandes grupos, com 6 ou mais células. A expressão da proteína NY-ESO-1 não esteve associada à idade, ao sexo, ao fototipo, ao sítio primário do tumor, à presença de ulceração, ao status do linfonodo sentinela, ao desenvolvimento de metástases ou à sobrevida. CONCLUSÕES: Há expressão de NY-ESO-1 em uma porcentagem considerável dos melanomas, principalmente nos mais espessos. O menor número de células CD3+ no infiltrado linfocítico tumoral, acrescido ao fato destas células estarem isoladas ou em pequenos grupos, sugere que embora imunogênico, a expressão do antígeno NY-ESO-1 não resulta num estímulo eficaz do sistema imune no combate ao tumor. O desenvolvimento de uma vacina para estes pacientes poderá, no futuro, aumentar as possibilidades terapêuticas do melanoma

Interactive effects of MC1R and OCA2 on melanoma risk phenotypes

The relationships between MC1R gene variants and red hair, skin reflectance, degree of freckling and nevus count were investigated in 2331 adolescent twins, their sibs and parents in 645 twin families. Penetrance of each MC1R variant allele was consistent with an allelic model where effects were multiplicative for red hair but additive for skin reflectance. Of nine MC1R variant alleles assayed, four common alleles were strongly associated with red hair and fair skin (Asp84Glu, Arg151Cys, Arg160Trp and Asp294His), with a further three alleles having low penetrance (Val60Leu, Val92Met and Arg163Gln). These variants were separately combined for the purposes of this analysis and designated as strong 'R' (OR=63.3; 95% CI 31.9-139.6) and weak 'r ' (OR=5.1; 95% CI 2.5-11.3) red hair alleles. Red-haired individuals are predominantly seen in the R/R and R/r groups with 67.1 and 10.8%, respectively. To assess the interaction of the brown eye color gene OCA2 on the phenotypic effects of variant MC1R alleles we included eye color as a covariate, and also genotyped two OCA2 SNPs (Arg305Trp and Arg419Gln), which were confirmed as modifying eye color. MC1R genotype effects on constitutive skin color, freckling and mole count were modified by eye color, but not genotype for these two OCA2 SNPs. This is probably due to the association of these OCA2 SNPs with brown/green not blue eye color. Amongst individuals with a R/R genotype (but not R/r), those who also had brown eyes had a mole count twice that of those with blue eyes. This suggests that other OCA2 polymorphisms influence mole count and remain to be described.

Expression and localization of mutant p16 proteins in melanocytic lesions from familial melanoma patients

Little is known about the correlation between the loss of p16 expression and tumor progression in familial melanoma; no systematic study has been conducted on p16 expression in melanocytic tumors from patients carrying germline CDKN2A mutations. We analyzed 98 early primary lesions from familial patients, previously tested for germline CDKN2A status, by quantitative immunohistochemistry using 3 p16 antibodies. We found that p16 expression was inversely correlated with tumor progression and was significantly lower in melanomas,. including in situ lesions, than in nevi. Of other features analyzed, tumor thickness showed the most significant correlation with p16 levels. Lesions from mutation-negative patients displayed combined nuclear and cytoplasmic staining. However, some mutation-positive lesions (ie, G101W, 113insR, M53I, R24P, and 33ins24), including benign nevi, showed nuclear mislocalization, confirming previous studies suggesting that subcellular distribution indicates functional impairment of p16. (C) 2004 Elsevier Inc. All rights reserved.

Trends for in situ and invasive melanoma in Queensland, Australia, 1982-2002

Objectives Queensland, the north-eastern state of Australia, has the highest incidence of melanoma in the world. Control measures started earlier here than probably anywhere else in the world; early detection programmes started in the 1960s and primary prevention in the 1980s. Data from the population-based Queensland Cancer Registry therefore provide an internationally unique data source with which to assess trends for in situ and invasive melanomas and to consider the implications for early detection and primary prevention. Methods We used Poisson regression to estimate the annual percentage change in rates across 21 years of incidence data for in situ and invasive lesions, stratified by age and sex. Joinpoint analyses were used to assess whether there had been a statistically significant change in the trends. Results In situ melanomas increased by 10.4% (95% CI: 10.1%, 11.1%) per year among males and 8.4% (7.9%, 8.9%) per year among females. The incidence of invasive lesions also increased, but not as quickly; males 2.6% (2.4%, 2.8%), females 1.2% (0.9%, 1.5%). Valid data on thickness was only available for 1991 to 2002 and for this period thin-invasive lesions were increasing faster than thick-invasive lesions (for example, among males: thin 3.8%, thick 2.0%). We found some suggestive evidence of lower proportionate increase for the most recent years for both in-situ and invasive lesions, but this did not achieve statistical significance. Among people younger than 35 years, the incidence of invasive melanoma was stable and there was a suggestion of a birth cohort effect from about 1958. Mortality rates were stable across all ages, and there was a suggestion of decreasing rates among young women, although this did not achieve statistical significance. Conclusion Age-standardised incidence is continuing to increase and this, in combination with a shift to proportionately more in situ lesions, suggests that the stabilisation of mortality rates is due, in large part, to earlier detection. For primary prevention, after a substantial period of sustained effort in Queensland, there is some suggestive, but not definitive, evidence that progress is being made. Incidence rates are stabilising in those younger than 35 years and the proportionate increase for both in situ and invasive lesions appears to be lower for the most recent period compared with previous periods. However, even taking the most favourable view of these trends, primary prevention is unlikely to lead to decreases in the overall incidence rate of melanoma for at least another 20 years. Consequently, the challenge for primary prevention programmes will be to maintain momentum over the long term. If this can be achieved, the eventual public-health benefits are likely to be substantial.

Clinical whole-body skin examination reduces the incidence of thick melanomas

Survival from melanoma is strongly related to tumour thickness, thus earlier diagnosis has the potential to reduce mortality from this disease. However, in the absence of conclusive evidence that clinical skin examination reduces mortality, evidence-based assessments do not recommend population screening. We aimed to assess whether clinical whole-body skin examination is associated with a reduced incidence of thick melanoma and also whether screening is associated with an increased incidence of thin lesions (possible overdiagnosis). A population-based case-control study of all Queensland residents aged 20-75 years with a histologically confirmed first primary invasive cutaneous melanoma diagnosed between January 2000 and December 2003. Telephone interviews were completed by 3,762 eligible cases (78.0%) and 3,824 eligible controls (50.4%) Whole-body clinical skin examination in the three years before diagnosis was associated with a 14% lower risk of being diagnosed with a thick melanoma (>0.75mm) (OR= 0.86, 95% CI=0.75, 0.98). Risk decreased for melanomas of increasing thickness: the risk of being diagnosed with a melanoma 0.76-1.49mm was reduced by 7% (OR=0.93, 95% CI 0.79, 1.10), by 17% for melanomas 1.50-2.99mm (OR=0.83, 95% CI=0.65, 1.05) and by 40% for melanomas ≥3mm (OR=0.60, 95% CI=0.43, 0.83). Screening was associated with a 38% higher risk of being diagnosed with a thin invasive melanoma (≤0.75mm) (OR=1.38, 95% CI=1.22, 1.56). This is the strongest evidence to date that whole-body clinical skin examination reduces the incidence of thick melanoma. Because survival from melanoma is strongly related to tumour thickness, these results suggest that screening would reduce melanoma mortality.

Component-wise gradient boosting and false discovery control in survival analysis with high-dimensional covariates.

MOTIVATION: Technological advances that allow routine identification of high-dimensional risk factors have led to high demand for statistical techniques that enable full utilization of these rich sources of information for genetics studies. Variable selection for censored outcome data as well as control of false discoveries (i.e. inclusion of irrelevant variables) in the presence of high-dimensional predictors present serious challenges. This article develops a computationally feasible method based on boosting and stability selection. Specifically, we modified the component-wise gradient boosting to improve the computational feasibility and introduced random permutation in stability selection for controlling false discoveries. RESULTS: We have proposed a high-dimensional variable selection method by incorporating stability selection to control false discovery. Comparisons between the proposed method and the commonly used univariate and Lasso approaches for variable selection reveal that the proposed method yields fewer false discoveries. The proposed method is applied to study the associations of 2339 common single-nucleotide polymorphisms (SNPs) with overall survival among cutaneous melanoma (CM) patients. The results have confirmed that BRCA2 pathway SNPs are likely to be associated with overall survival, as reported by previous literature. Moreover, we have identified several new Fanconi anemia (FA) pathway SNPs that are likely to modulate survival of CM patients. AVAILABILITY AND IMPLEMENTATION: The related source code and documents are freely available at https://sites.google.com/site/bestumich/issues. CONTACT: yili@umich.edu.

Mfge8 Expression In Conjunctival Melanocytic Proliferations

Purpose: Milk fat globule epidermal growth factor-8 (MFGE8) is a secreted phosphatidylserine-binding protein that has been involved in phagocytosis, as well as in VEGF dependent neovascularization. In a study evaluating protein expression in membrane rafts of cutaneous melanoma at different stages of progression, MFGE8 expression was only identified in membrane rafts of metastatic cutaneous melanoma cell lines. Furthermore, MFGE8, identified at higher level in the vertical growth phase of cutaneous melanoma, promoted tumor growth in vivo, enhanced invasion in vitro and metastatic spread in a mouse model. The purpose of this study was to assess the expression of MFGE8 in conjunctival melanocytic proliferations.Methods: MFGE8 expression was assessed by immunohistochemistry in 66 melanocytic conjunctival proliferations including 21 conjunctival naevi, 20 Primary Acquired Melanosis (PAM) including (4 PAM without atypia and 16 PAM with atypia) and 25 conjunctival melanomas. Expression was independently assessed by 2 pathologists. Relevant clinico-pathological data were retrieved. Statistical anaylis was performed using JUMP 8 software.Results: The concordance between the 2 pathologists had an 87,5% agreement on the first independent assessment of MFGE8 expression. Complete agreement was further reached after joint revision of discordant cases. In the naevi, MFGE8 expression was found in only 4 cases (3 subepithelial cases and 1 composed combined naevus). In the PAM group, MFGE8 was identified in 1 PAM without atypia and 10 PAM with atypia. In the melanoma group, MFGE8 expression was observed in 68% of cases. The expression of MFGE8 in the conjunctival melanocytic proliferation was significantly higher in the melanoma (p=0,0009) and in the PAM (p=0,0169) than in naevi. Within the PAM subgroup, we found no significant correlation between MFGE8 expression and the presence of atypia in the respective specimen examined so far.Conclusions: We demonstrate a significant higher expression of MFGE8 in conjunctival melanoma compared to benign melanocytic lesions, suggesting that this protein may play a role in tumor progression of conjunctival melanocytic proliferations. Further experimental studies should be performed to better characterize MFGE8 involvement in conjunctival melanoma tumorigenesis.

Resultados del tratamiento de nevos melanocíticos con láser

Introducción A pesar de que los nevos melanocíticos son un motivo de consulta frecuente en nuestra población no existen estudios a nivel de Colombia acerca de su tratamiento, a nivel mundial existe muy poca literatura al respecto por lo que hay un vacío conceptual en este campo. Objetivos Evaluar los cambios en cuanto a la presencia de pigmento y cicatrización, en los nevos melanocíticos adquiridos tratados con láser, basados en la experiencia de un solo centro en Bogotá. Materiales y métodos Es un estudio observacional de antes y después, en una cohorte histórica, de 90 casos de nevos melanocíticos adquiridos, tratados con láser en Uniláser Medica, en los que se evaluó la presencia de pigmento, cicatrización, y otras variables, con un control realizado a no menos de 3 meses de la intervención. Resultados Se encontró un rango de edad entre los 18 -51 años, promedio 27,59 años; fototipo de III-V; en el 32% de los casos, solo fue requerida una sesión de láser de Co2 y Erbio, para el aclaramiento completo de la misma. La duración del eritema en el 54,4% los casos fue de 1 a 3 meses. En un 64,4% quedó pigmento residual al control, pero de éstos casos el 48,2% fue entre un 5 a un 10% del inicial. El 58,9% hizo cicatriz, de éstos el 63% fue estética. La satisfacción por parte de los pacientes es alta a pesar de la persistencia pigmentaria y/o la presencia de cicatriz. Discusión El tratamiento de nevos melanocíticos adquiridos con láser es una opción terapéutica que genera cambios estadísticamente significativos en cuanto a pigmento, cicatriz estética y alta satisfacción por parte de los pacientes. Se requieren estudios, analíticos, para determinar eficacia del tratamiento.

Estudo da precocidade diagnóstica dos melanomas cutâneos primários em Porto Alegre por análise de imagem computadorizada

Fundamentos: A literatura tem demonstrado que a detecção precoce e a remoção cirúrgica em fases iniciais reduz a mortalidade do melanoma e que, em conseqüência, a identificação do melanoma em fases curáveis deve ser encorajada. Objetivos: O interesse principal do estudo foi conhecer se os melanomas cutâneos, no meio, estão sendo diagnosticados em fases iniciais, através de método reprodutível e armazenável. Metodologia: Foi realizado um estudo transversal com os casos de melanomas cutâneos primários, analisados nos laboratórios de patologia de Porto Alegre, de 1° de janeiro de 1994 a 30 de junho de 1995, a fim de avaliar se os diagnósticos foram realizados em estágios precoces. Os casos foram revisados por três dermatopatologistas, que classificaram quanto ao tipo histológico e quanto ao nível de invasão de Clark. Foi realizado um consenso com pelo menos duas concordâncias. A espessura de Breslow foi considerada fator prognóstico determinante e foi medida através de um sistema de análise de imagem computadorizada, por dois membros da equipe. Resultados: Do total de 279 casos que preencheram os critérios de inclusão, 2,15% eram intraepiteliais. Dos melanomas invasivos, 52% tinham espessura ≤ 1,5 mm. Quando agrupado por sexo e procedência, as mulheres de Porto Alegre, capital do estado do Rio Grande do Sul, tiveram a mais alta taxa de diagnóstico precoce (75% ≤ 1,5 mm). O tronco foi o sítio predominante no homem e freqüente na mulher. O melanoma de espalhamento superficial foi o tipo histológico mais freqüente (80,9%), seguido pelo nodular (10,1%). Para definir os determinantes do diagnóstico precoce, foram realizados cruzamentos simples, dos melanomas intraepiteliais somados aos de espessura <0,76 mm, com o sexo, a idade, a procedência, a situação previdenciária, a região anatômica e o tipo histológico. A análise de variáveis múltiplas demonstrou que apenas o sexo (feminino), o sítio anatômico (outras regiões exceto membros inferiores) e a procedência (Porto Alegre) mostraram-se variáveis independentes para determinar um diagnóstico precoce. A idade ≥ 40 anos apresentou significância próxima ao limite. O tipo histológico foi excluído do modelo, uma vez que gerou instabilidade estatística. Conclusão: Embora o número de casos fosse pequeno, o diagnóstico do melanoma ainda é tardio (52% com até 1,5 mm de espessura). Entretanto, existe um subgrupo de diagnóstico precoce que são mulheres, sobretudo de Porto Alegre, possivelmente por estarem mais atentas e informadas sobre os riscos do melanoma. As mudanças no estilo de vida, nas últimas décadas, provavelmente são responsáveis pela maior incidência no tronco e pela alta freqüência de melanoma de espalhamento superficial encontrada. A análise da espessura tumoral por projeção em tela de computador mostrou-se um recurso auxiliar vantajoso.

Efeitos da radiação ultravioleta b na expressão imunoistoquímica das metaloproteinases –2 e –9 em nevos melanocíticos

Introdução: a incidência dos melanomas permanece em ascensão em diversos países. Os nevos melanocíticos podem ser seus precursores ou marcadores de risco. A radiação ultravioleta é o principal fator de risco ambiental para o seu desenvolvimento. Estudos com nevos irradiados mostram que a radiação ultravioleta B (UVB) pode causar alterações morfológicas e bioquímicas semelhantes às de um melanoma in situ. As metaloproteinases da matriz (MMP) são enzimas proteolíticas e, particularmente, as MMP-2 e –9 (gelatinases A e B) parecem estar associadas à invasão tumoral, à formação de metástases e de neoangiogênese em melanomas. O objetivo do presente estudo é avaliar os efeitos da UVB nas expressões imunoistoquímicas de MMP-2 e –9 nas diferentes linhagens celulares de nevos melanocíticos. Métodos: quarenta e dois nevos melanocíticos tiveram suas metades irradiadas com dose de 2 DEM (dose eritematosa mínima) de UVB e foram excisados uma semana após. As expressões imunoistoquímicas das MMP-2 e -9 foram comparadas, quanto à sua intensidade, por três avaliadores diferentes entre os lados irradiados e não irradiados em queratinócitos, melanócitos de epiderme e derme superior, células endoteliais e fibroblastos. Os dados foram analisados pelo teste t pareado para as diferenças de expressão e pelo ICC para avaliação da homogeneidade entre as respostas dos observadores. Resultados: com relação à expressão imunoistoquímica de MMP-2, todas as linhagens celulares mostraram aumento no lado irradiado, especialmente os melanócitos epidérmicos. Quanto à MMP-9, somente nos queratinócitos, não se observou aumento de expressão do lado irradiado, ficando essa evidente nas demais linhagens celulares avaliadas. Conclusões: A UVB na dose de 2 DEM aumenta a expressão imunoistoquímica das MMP-2 e –9 em quase todas as linhagens celulares dos nevos melanocíticos avaliados até uma semana após a irradiação, com exceção feita queratinócitos, com a MMP-9.

Análise da expressão protéica de moléculas de adesão celular em melanomas cutâneos

Cutaneous melanoma is a malignancy caused by the uncontrolled proliferation of melanocytes. Has been increasing in incidence and mortality over the years. This type of tumor may arise in the skin or any other place where there was migration of neural crest cells. Melanocytes are located in the basal layer of the epidermis forming the epidermal melanin unit, involving a melanocyte to 36 keratinocytes. The proliferation of melanocytes depends on this relationship with the keratinocytes, gap junctions, E-cadherin and desmoglein. The basal membrane is responsible for promoting the integrity of the skin, their adhesion structures shown to be altered in several skin diseases. Some molecules that play the role of adherence in this membrane are the laminins, type IV collagen and type XVII and perlecan. Analysis of protein expression of cell adhesion molecules in melanoma by immunohistochemistry on tissue microarray (TMA). We selected paraffin blocks of patients who were diagnosed with cutaneous melanoma in the period 1995 to 2010, reaching a sample of 124 cases. All these have gone through review of preparation for subsequent histological analysis of tissue microarray (TMA). The protein expression will be analyzed by immunohistochemistry, using markers anti-laminin, anti-collagen type IV and type XVII and anti-perlecan. There was a predominance of female patients, Caucasians and southeastern Brazil. There were frequent in type of extensive superficial ulcers with Breslow depth greater than 4 mm, Clark level IV and mitotic index greater than 6 mitoses per cga. The patients, most of them were female with mean age of 57.13 years and Caucasian. The most frequent histological type was extensive superficial followed by acral lentiginous. Predominated cases very deep, with Breslow thickness greater than 4 mm, Clark IV, ulcerated and on average by 9 cga mitosis, leading to worse prognosis in this sample. It...(Complete abstract click electronic access below)

UV Responses in Native Hawaiians or Other Pacific Islanders and Asians Residing in Hawaiʻi and in Maryland

Background: UV exposure causes a wide range of skin damage including cutaneous melanoma. The mechanisms of cellular and molecular damage as well as erythemal and pigmentation responses to UV exposure have largely been studied in the White population. Methods: This study systematically investigates responses to UV exposure in the Native Hawaiian and Pacific Islanders (NHPI) and Asian populations living in Hawai’i (A/HI) as well as in Asians living in Maryland (A/MD). Results: Our analyses indicate that the NHPI population is less sensitive to UV exposure than the A/HI population. Comparisons between the two Asian groups suggest that, despite slightly but not statistically different baseline constitutive pigmentation (pre-UV exposure), the A/HI and A/MD had similar UV sensitivity, measured as minimal erythemal dose (MED). However, the A/MD population had higher levels of oxy-hemoglobin at doses of 2.0, 2.8 and 4.0 MED. Unexpectedly the A/MD subjects retained higher levels of pigmentation 2 weeks post UV exposure. Conclusion: This study provides insight into UV responses of the inhabitants of Hawai’i and shows that such responses are statistically significant for relatively small samples of Native Hawaiian and Pacific Islanders, and for Asians living in Hawai’i and Asians living in Maryland.