RESUMO
DEK is an oncoprotein involved in a variety of cellular functions, such as DNA repair, replication, and transcriptional control. DEK is preferentially expressed in actively proliferating and malignant cells, including melanoma cell lines in which DEK was previously demonstrated to play a critical role in proliferation and chemoresistance. Still, the impact of this protein in melanoma progression remains unclear. Thus, we performed a comprehensive analysis of DEK expression in different melanocytic tumors. The immunostaining results of 303 tumors demonstrated negligible DEK expression in benign lesions. Conversely, malignant lesions, particularly in metastatic cases, were largely positive for DEK expression, which was partially associated with genomic amplification. Importantly, DEK overexpression was correlated with histological features of aggressiveness in primary tumors and poor prognosis in melanoma patients. In conclusion, our study provides new insight into the involvement of DEK in melanoma progression, as well as proof of concept for its potential application as a marker and therapeutic target of melanoma.
Assuntos
Biomarcadores Tumorais/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Regulação Neoplásica da Expressão Gênica , Melanoma/patologia , Proteínas Oncogênicas/metabolismo , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , Biomarcadores Tumorais/genética , Proliferação de Células , Proteínas Cromossômicas não Histona/genética , Progressão da Doença , Feminino , Seguimentos , Humanos , Técnicas Imunoenzimáticas , Metástase Linfática , Masculino , Melanoma/genética , Melanoma/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Oncogênicas/genética , Proteínas de Ligação a Poli-ADP-Ribose/genética , Prognóstico , Taxa de Sobrevida , Células Tumorais CultivadasRESUMO
The era of targeted therapy has introduced a new therapeutic perspective for melanoma patients. Treatment with BRAFV600 inhibitors has improved overall and disease-free survival in metastatic melanoma patients whose tumors harbor BRAFV600 mutations. Although the BRAFV600E mutation appears to have a critical role in tumor initiation, its expression during tumor progression remains controversial. In fact, various authors claim that BRAFV600E heterogeneity is evident in melanoma tumors. Herein, we investigated the pattern of BRAFV600E expression in matched primary and metastatic samples from 140 patients. Using a combination of real-time PCR and immunohistochemical analyses, we demonstrated that BRAFV600E expression is homogeneous in melanoma tumors and hypothesized that the heterogeneity described by others might be attributable to technical issues when molecular methods are used. We also demonstrated the high efficiency of the anti-BRAFV600E VE1 antibody for the detection of BRAFV600E mutations in melanoma tumors.