Cytoplasmic Skp2 Expression Is Increased in Human Melanoma and Correlated with Patient Survival

BACKGROUND: S-phase kinase protein 2 (Skp2), an F-box protein, targets cell cycle regulators via ubiquitin-mediated degradation. Skp2 is frequently overexpressed in a variety of cancers and associated with patient survival. In melanoma, however, the prognostic significance of subcellular Skp2 expression remains controversial. METHODS: To investigate the role of Skp2 in melanoma development, we constructed tissue microarrays and examined Skp2 expression in melanocytic lesions at different stages, including 30 normal nevi, 61 dysplastic nevi, 290 primary melanomas and 146 metastatic melanomas. The TMA was assessed for cytoplasmic and nuclear Skp2 expression by immunohistochemistry. The Kaplan-Meier method was used to evaluate the patient survival. The univariate and multivariate Cox regression models were performed to estimate the hazard ratios (HR) at five-year follow-up. RESULTS: Cytoplasmic but not nuclear Skp2 expression was gradually increased from normal nevi, dysplastic nevi, primary melanomas to metastatic melanomas. Cytoplasmic Skp2 expression correlated with AJCC stages (I vs II-IV, P<0.001), tumor thickness (≤2.00 vs >2.00 mm, P<0.001) and ulceration (P = 0.005). Increased cytoplasmic Skp2 expression was associated with a poor five-year disease-specific survival of patients with primary melanoma (P = 0.018) but not metastatic melanoma (P>0.05). CONCLUSION: This study demonstrates that cytoplasmic Skp2 plays an important role in melanoma pathogenesis and its expression correlates with patient survival. Our data indicate that cytoplasmic Skp2 may serve as a potential biomarker for melanoma progression and a therapeutic target for this disease

Raça e o uso dos serviços de saúde bucal por idosos Race and the use of dental health services by the elderly

Analisamos se a raça pode ser considerada um fator limitante na utilização dos serviços odontológicos por idosos. O presente estudo é de caráter analítico, com a utilização de dados secundários coletados pela Pesquisa Nacional de Saúde Bucal em 2003. Foram incluídos os examinados que se declararam como brancos, pardos ou pretos, na faixa etária de 65 a 74 anos. O número amostral foi composto por 5.108 idosos sendo 2.575 brancos e 2.533 negros. Dos brancos 3,8% afirmaram nunca terem ido ao dentista enquanto que para os negros esse valor é de 7,8%. Mesmo após o ajuste com interceptação de necessidade de prótese e dor, a chance do idoso negro não ter utilizado o serviço odontológico pelo menos uma vez na vida é 0.62 OR menor que para um idoso branco. Dos que utilizaram os serviços, 21,2% dos idosos brancos visitaram o dentista no último ano, enquanto para os negros o valor foi de 14,2%, no modelo ajustado interceptado pela necessidade de prótese e dor o OR foi de 0.60. Todas as relações foram estatisticamente significantes (p < 0,001). A raça é um fator limitante na utilização dos serviços odontológicos por idosos e, mesmo após ajustes, os idosos negros permanecem com maior dificuldade na utilização dos serviços de saúde bucal.<br>We analyze if race can be considered a limiting factor in the use of dental services by the elderly. This study is of an analytical nature, with the use of secondary data collected by the National Survey of Oral Health in 2003. Those examined who declared themselves as being white, brown or black in the 65 to 74-year-old age bracket were included. The sample was composed of 5,108 elderly people: 2,575 whites and 2,533 blacks. Of the whites, 3.8% stated that they had never been to the dentist, while this figure was 7.8% for the blacks. Even after the adjustment for interception for prosthetics and dental pain, the chance of elderly blacks not having used dental services at least once in their life is 0.62 OR less than for elderly whites. Of those who used the services, 21.2% of the elderly whites visited the dentist in the last year, while for elderly blacks the figure was 14.2%, in the adjusted model for interception for prosthetics and dental pain the OR was 0.60. All the relations were statistically significant (p<0,001). Race is a limiting factor in the use of dental services by the elderly and even after the adjustments the elderly blacks continue to manifest greater resistance to the use of oral health services