Skin pigmentation polymorphisms associated with increased risk of melanoma in a case-control sample from southern Brazil.

BACKGROUND: Melanoma is the most aggressive type of skin cancer and is associated with environmental and genetic risk factors. It originates in melanocytes, the pigment-producing cells. Single nucleotide polymorphisms (SNPs) in pigmentation genes have been described in melanoma risk modulation, but knowledge in the field is still limited. METHODS: In a case-control approach (107 cases and 119 controls), we investigated the effect of four pigmentation gene SNPs (TYR rs1126809, HERC2 rs1129038, SLC24A5 rs1426654, and SLC45A2 rs16891982) on melanoma risk in individuals from southern Brazil using a multivariate logistic regression model and multifactor dimensionality reduction (MDR) analysis. RESULTS: Two SNPs were associated with an increased risk of melanoma in a dominant model: rs1129038AA and rs1426654AA [OR = 2.094 (95% CI: 1.106-3.966), P = 2.3 10- 2 and OR = 7.126 (95% CI: 1.873-27.110), P = 4.0 10- 3, respectively]. SNP rs16891982CC was associated with a lower risk to melanoma development in a log-additive model when the allele C was inherited [OR = 0.081 (95% CI: 0.008-0.782), P = 3 10- 2]. In addition, MDR analysis showed that the combination of the rs1426654AA and rs16891982GG genotypes was associated with a higher risk for melanoma (P = 3 10- 3), with a redundant effect. CONCLUSIONS: These results contribute to the current knowledge and indicate that epistatic interaction of these SNPs, with an additive or correlational effect, may be involved in modulating the risk of melanoma in individuals from a geographic region with a high incidence of the disease.

Dermatoscopic Patterns of Nonfacial Actinic Keratosis: Characterization of Pigmented and Nonpigmented Lesions.

BACKGROUND: Actinic keratoses (AKs) are dysplastic proliferations of keratinocytes. Studies evaluating nonfacial dermatoscopic pattern of AKs are scarce. OBJECTIVE: This study aimed to evaluate the dermatoscopic patterns of AKs located in nonfacial sites and to compare their patterns with facial lesions. MATERIALS AND METHODS: Patients with concomitant facial and nonfacial AKs were recruited to participate and evaluated by clinical and dermatoscopic images of their AKs. RESULTS: Sixty-eight patients were included in the study. A total of 258 nonfacial AKs and 68 facial AKs were analyzed. The most frequent nonfacial AK dermatoscopic structures were white opaque scales (97.3%) and erythema (57.4%). When analyzed in combination, white scales plus erythema were found in 55.4% of nonfacial AKs. Pigmented structures were observed in 22.5% nonfacial AKs. Homogeneous brown pigmentation was the most prevalent pigmented structure in nonfacial pigmented AK (pAK) (93.1%). There was a positive association between patients having concomitant pigmented facial and nonfacial AKs (p < .001). CONCLUSION: The combinations of erythema and white opaque scales or yellow opaque scales and homogeneous pigmentation are suggestive, respectively of nonpigmented and pigmented nonfacial AKs. Pigmented AKs occur concomitantly in facial and nonfacial areas.

Skin cancer characteristics during the first year of the COVID-19 pandemic at a tertiary hospital in Latin America.

BACKGROUND: The influence of the novel human coronavirus disease (COVID-19) pandemic on skin cancer characteristics in Latin America is still poorly elucidated. METHODS: This was a cross-sectional study which included patients diagnosed with skin cancer (basal cell carcinoma [BCC], cutaneous squamous cell carcinoma [cSCC], and primary cutaneous melanoma [cMM]) during the first year of the COVID-19 pandemic (from March 1, 2020, to February 28, 2021) and the preceding year at our institution. The total number of skin cancer diagnoses and surgeries, as well as their topography, clinicopathological staging at diagnosis, and treatment delay were compared between the two periods. RESULTS: There was a 31.8% reduction in skin cancer diagnoses during the first year of the COVID-19 pandemic at our institution. There was an increase in the proportion of low-risk cancers according to the NCCN guidelines for BCCs (40.8-49%, P < 0.001) and cSCCs (41.7-49.6%, P = 0.03), but there was no difference in the distribution of other staging systems for the three types of cancer. We also found a significant reduction in surgeries for BCCs (-57.6%, P < 0.001) and cSCCs (-44.7%, P < 0.001) but not for cMM. CONCLUSIONS: The first year of the COVID-19 pandemic was associated with reduced numbers of skin cancer diagnoses and surgeries at our institution. This study provides an assessment of skin cancer characteristics during the first year of the pandemic in the Latin American population.

The CDKN2A p.A148T variant is associated with cutaneous melanoma in Southern Brazil.

Several germline mutations and sequence variants in cancer predisposition genes have been described. Among these, the CDKN2A p.A148T variant appears to be frequent in patients with melanoma, at least in certain ethnic groups. In this case-control study, we evaluated 127 patients with cutaneous melanoma and 128 controls from Southern Brazil, the region with the highest melanoma incidence rates in the country. Using PCR-RFLP, we demonstrate that CDKN2A p.A148T variant was significantly more frequent in patients with melanoma than in controls (12.6% vs 3.9%; P=0.009). There was no association between presence of the polymorphism and tumor thickness, site of the primary tumor, melanoma subtype, age at diagnosis, quantitative and qualitative number of nevi. Patients with a positive family of history for other cancers were particularly prone to carry the CDKN2A p.A148T allele. All patients with p.A148T-positive melanoma reported European ancestry, especially German, and this was confirmed using a panel of ancestry-informative INDELs. Our data suggest that CDKN2A p.A148T is a melanoma susceptibility allele in Southern Brazil and is particularly common in patients with melanoma of predominantly European ancestry.

Nestin and SOX9 and SOX10 transcription factors are coexpressed in melanoma.

Nestin is an intermediate filament expressed in proliferating neural progenitor cells and has been considered as a stem cell marker. Nestin is also found in melanoma and we recently demonstrated that its expression in melanoma cell lines is regulated by the transcription factors SOX9 and SOX10, but not BRN2. In this study, the expression levels of nestin, BRN2, SOX9 and SOX10 were analysed in tissues of melanoma (n = 78) and melanocytic nevi (n = 26) by immunohistochemistry. All proteins were highly expressed in primary and metastatic melanomas and, apart from BRN2, showed much lower levels in melanocytic nevi. Significant coexpression of nestin with SOX9 and SOX10 was found in primary melanoma confirming our in vitro data. Correlation analysis with clinicopathological data revealed that nestin was significantly associated with presence of ulceration in primary tumors and SOX9 with more advanced stage of disease. Our data reveal that SOX9 and SOX10 are highly expressed in melanoma and seem to have a regulatory role in nestin expression. The association with ulceration and advanced-stage tumors, respectively, suggests that nestin and SOX9 may be negative prognostic markers in melanoma.

[A rare case of local relapsing oral melanoma]. / Ein seltener Fall eines lokal rezidivierenden oralen Melanoms.

Melanoma of the oral mucosa is an extremely rare tumor. At the time of diagnosis most melanomas are in an advanced stage because of few clinical signs. Therefore the prognosis of melanoma of the oral mucosa is often very poor. We present a 48-year-old patient with melanoma of the oral mucosa first diagnosed 22 years ago. Over 20 years several wide excisions were necessary because of multiple local relapses. Eventually, the patient died from brain metastases.

Polymorphisms in CYP19A1 and NFKB1 genes are associated with cutaneous melanoma risk in southern Brazilian patients.

BACKGROUND: Melanoma is the leading cause of death from skin cancers and its etiology is complex. Recent discoveries related to genetic risk factors are helping us to understand melanoma pathogenesis better. Nuclear factor-κB (NF-κB) has a critical role in immunity, inflammation, and tumor growth. The 94ins/del ATTG (rs28362491) polymorphism located in the NFKB1 gene has been associated to various cancers and the ATTG2/ATTG2 genotype was correlated to melanoma risk in Sweden. The CYP19A1 gene encodes the enzyme aromatase, which is active in malignant melanoma tissue. In addition, the CYP19A1 TCT insertion/deletion variant in intron 4 (rs11575899) has been associated with an increased incidence of cancer, albeit with conflicting results. The goal of this study was to investigate possible associations between these two gene variants and melanoma. METHODS: In this case-control study, we evaluated 117 cutaneous melanoma patients and 116 controls from southern Brazil. Genotyping of rs28362491 and rs11575899 was carried out by means of PCR amplification and capillary electrophoresis. Logistic regression was used to obtain odds ratios (ORs) of melanoma, according to genotypes. RESULTS: We identified an association between the ATTG2/ATTG2 and melanoma [OR=1.78; 95% confidence interval (CI): 1.06-3.00; P=0.03]. In addition, there was a dose effect: for each ins allele in the genotype, the risk for melanoma increased (OR=1.51; 95% CI: 1.08-2.11; P=0.017). As regards the CYP19A1 variant, genotype 11 (del/del) was more frequent in patients than in controls (OR=1.85; 95% CI 1.06-3.22; P=0.03). CONCLUSION: The NFKB1 ATTG2/ATTG2 and CYP19A1 del/del genotypes are significantly associated with melanoma and could be genetic markers of melanoma susceptibility in southern Brazilian population.

Sunburn, sunscreens, and phenotypes: some risk factors for cutaneous melanoma in southern Brazil.

BACKGROUND: The risk factors for cutaneous malignant melanoma have been studied in populations from numerous countries around the world. There are no published studies on the risk factors for this malignancy in Brazil, the largest country in South America. METHODS: A case-control study of all melanoma patients attending a university hospital in Porto Alegre, Brazil, was conducted over a 3-year period from 1995 to 1998. Phototype, hair and eye color, solar habits, history of sunburn, use of sunscreens, and the number of nevi were evaluated through a questionnaire and full body skin examination. Bivariate analysis and a logistic regression model were used to evaluate the data. RESULTS: One hundred and three malignant melanoma patients and 206 matched controls were enrolled in the study. The female to male ratio was 2 : 1. Light phototypes were more prone to the development of cutaneous melanoma. Although stronger in the bivariate analysis, in the logistic regression model, phototypes I or II and ephelides emerged only as moderate risk factors; light eye color and light hair color were not independently significant, with adjusted odds ratios (OR) close to zero. Commonly acquired nevi (CAN) showed a significant and strong effect in the bivariate analysis only when the "30 or more" category was compared to baseline. In the logistic regression model, the presence of a large number of CAN showed an association with increased levels of risk, although these findings did not reach classical significance. Dysplastic or atypical nevi seemed to contribute more strongly, although still with a moderate excess of relative risk. When the use of sunscreens was compared to no use at all, it appeared to show progressive protection as the solar protection factor (SPF) increased. Only SPF15 or greater (SPF15+) showed strong and significant protection when compared to baseline. Physical measures offered a weaker level of protection. Nevertheless, there was a significant increase in the risk of melanoma for those with a large number of sunburn episodes. It was found that 30 or more alleged episodes of sunburn showed a very strong OR of 11.4 (95% confidence interval, 2.6-50.5), the most significant in the study. CONCLUSIONS: Phototypes I and II, freckles, a large number of acquired nevi, dysplastic nevi, and inadequate photoprotection appeared as risk factors with moderate strength for cutaneous malignant melanoma in the studied population. The color of the eyes and hair showed a very weak statistical significance as a risk factor. Sunscreens showed progressive significance corresponding to an increase in SPF, the best scores in statistical protection being achieved in users of sunscreens with SPF15 or greater. Frequent sunburn episodes appeared as the most important risk factor associated with malignant melanoma in this sample of the white population in southern Brazil.

Flutamida no tratamento da acne / Flutamide in acne treatment

FUNDAMENTOS - A flutamida é potente antiandrógeno näoö-esteróide, deprovido de outras propriedades hormonais ou näo-hormonais, utilizado no tratamento do câncer prostático avançado, e que possui marcada atividade no tratamento do hirsutismo e no bloqueio das glândulas sebáceas. OBJETIVOS - Avaliar a eficácia e segurança da flutamida oral em doses de 250mg/dia na acne näo responsiva aos tratamentos convencionais. MATERIAL E MÉTODOS - Trinta e oito mulheres voluntárias sadias, em idade fértil, com diferentes graus de intensidade de acne e níveis séricos de andrógenos normais foram tratadas com flutamida oral, 125mg/2x/dia por um período de até 18 meses, com acompanhamento clínico e laboratorial bimensal. RESULTADOS - Houve involuçäo total das lesöes clínicas em 34,2 porcento das pacientes, reduçäo de mais da metade da intensidade da acne em 47,4 porcento e reduçäo de menos de um terço das lesões em 7,8 porcento das pacientes. Em 10,6 porcento o quadro manteve-se inalterado ou até pior. Com essa dosagem, näo se observaram efeitos colaterais, clínicos ou laboratoriais, de monta. Após a suspensäo do fármaco, cerca de um terço das pacientes experimentou recidiva do quadro acnéico, com intensidades variáveis. CONCLUSÄO - Muito embora näo podendo ser considerada droga de rotina no tratamento da acne feminina, a flutamida pode constituir-se em alternativa terapêutica bastante útil no combate do hiperandrogenismo cutâneo para algumas pacientes selecionadas