RESUMO
ABSTRACT Background: Gastric cancer is the fifth most frequent cancer and the third most common cause of cancer-related deaths worldwide.It has been reported that Wnt/ betacatenin pathway is activated in 30-50% of these tumors. However,the deregulation of this pathway has not been fully elucidated. Aim: To determine the expression of E-cadherin, betacatenin, APC, TCF-4 and survivin proteins in gastric adenocarcinoma tissues and correlate with clinical and pathological parameters. Method: Seventy-one patients with gastric adenocarcinoma undergoing gastrectomy were enrolled. The expression of E-cadherin, betacatenin, APC, TCF-4 and survivin proteins was detected by immunohistochemistryand related to the clinical and pathological parameters. Results: The expression rates of E-cadherin in the membrane was 3%; betacatenin in the cytoplasm and nucleus were 23,4% and 3,1% respectively; APC in the cytoplasm was 94,6%; TCF-4 in the nucleus was 19,4%; and survivin in the nucleus 93,9%. The expression rate of E-cadherin was correlated with older patients (p=0,007), while betacatenin with tumors <5 cm (p=0,041) and APC with proximal tumors (p=0,047). Moreover, the expression of TCF-4 was significantly higher in the diffuse type (p=0,017) and T4 tumors (p=0,002). Conclusion: The Wnt/betacatenin is not involved in gastric carcinogenesis. However, the high frequency of survivin allows to suggest that other signaling pathways must be involved in the transformation of gastric tissue.
RESUMO Racional: O câncer gástrico encontra-se entre as principais neoplasias malignas do mundo sendo o quinto mais incidente e o terceiro em relação ao índice de mortalidade. Acredita-se que a via Wnt/betacatenina esteja ativada em 30-50% desses tumores, porém a desregulação dela ainda não está completamente esclarecida. Objetivo: Avaliar a imunoexpressão das proteínas E-caderina, betacatenina, APC, TCF-4 e survivina em tecidos de adenocarcinoma gástrico e correlacioná-las com as variáveis clínicas dos doentes e anatomopatológicas do tumor. Método: Foram coletados os dados clínicos e anatomopatológicos dos prontuários de 71 doentes com adenocarcinoma gástrico submetidos à gastrectomia. O material obtido na operação foi submetido à análise imunoistoquímica e a frequência da expressão de cada proteína pôde ser analisada de acordo com a sua localização na célula e relacionada com as variáveis clinicopatológicas. Resultados: A graduação percentualda expressão e da localização das proteínas foi a seguinte: E-caderina em 3% na membrana; betacatenina em 23,4% no citoplasma e 3,1% no núcleo; APC em 94,6% no citoplasma; TCF-4 em19,4% no núcleo; e survivina em 93,9% no núcleo. Houve relação entre expressão da proteína E-caderina com a idade mais avançada (p=0,007); betacatenina com tumores <5 cm de diâmetro (p=0,041);APC com tumores proximais (p=0,047); e TCF-4 com tipo difuso da classificação de Lauren (p=0,017) e com o grau de penetração tumoral (p=0,002). Conclusão: A via Wnt/betacatenina não está envolvida na carcinogênese gástrica. Porém, a frequência elevada de survivina permite sugerir que outras vias sinalizadoras devam estar envolvidas na transformação do tecido gástrico.
Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Gástricas/metabolismo , Adenocarcinoma/metabolismo , Caderinas/biossíntese , Proteínas Wnt/biossíntese , Fatores de Transcrição/biossíntese , Antígenos CD , Proteína da Polipose Adenomatosa do Colo/biossíntese , Proteínas Inibidoras de Apoptose/biossíntese , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/biossíntese , Via de Sinalização Wnt , Fator de Transcrição 4 , SurvivinaRESUMO
We report the case of a 58-year old patient, showing a solid image in the right kidney, who underwent radical nephrectomy that revealed neoplasia, whose pathological study led to the diagnosis of kidney carcinoma associated with Xp11.2 translocation / TFE3 (ASPL-TFE3) gene fusion. The authors discuss aspects related to this lesion, such as frequency, pathogenesis, clinical presentation, histopathology and outcome, as observed in the literature.
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Carcinoma de Células Renais/genética , Cromossomos Humanos X/genética , Proteínas de Ligação a DNA/genética , Neoplasias Renais/genética , Fatores de Transcrição/genética , Translocação Genética/genética , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos , Carcinoma de Células Renais/patologia , Neoplasias Renais/patologiaRESUMO
Exclusion of the transcription factor Max from the nucleus of retinal ganglion cells is an early, caspase-independent event of programmed cell death following damage to the optic axons. To test whether the loss of nuclear Max leads to a reduction in neuroprotection, we developed a procedure to overexpress Max protein in rat retinal tissue in vivo. A recombinant adeno-associated viral vector (rAAV) containing the max gene was constructed, and its efficiency was confirmed by transduction of HEK-293 cells. Retinal ganglion cells were accessed in vivo through intravitreal injections of the vector in rats. Overexpression of Max in ganglion cells was detected by immunohistochemistry at 2 weeks following rAAV injection. In retinal explants, the preparation of which causes damage to the optic axons, Max immunoreactivity was increased after 30 h in vitro, and correlated with the preservation of a healthy morphology in ganglion cells. The data show that the rAAV vector efficiently expresses Max in mammalian retinal ganglion cells, and support the hypothesis that the Max protein plays a protective role for retinal neurons.
