A high HIF-1α expression genotype is associated with poor prognosis of upper aerodigestive tract carcinoma patients

SummaryThe aim of the present study was to evaluate the role of HIF-1α genetic polymorphisms and protein expression in the development of metastasis in upper aerodigestive tract cancer (UADTC) patients. The expression of pro-angiogenic markers was also evaluated. Protein expression was analysed using immunohistochemistry, and RFLP analysis was used to investigate HIF-1α C1779T and G1790A polymorphisms in 52 patients with UADTC. Primary lesions were divided into 2 groups according to the absence or presence of metastasis. Lymph node samples were divided into 3 groups: metastatic lymph nodes, non-metastatic lymph nodes (both derived from patients with metastatic disease), and control lymph nodes, which were obtained from patients without any metastasis. The allele T was more frequently found in patients with metastatic disease. HIF-1α protein expression in the lymph nodes was increased in the presence of the T allele. Metastatic lymph nodes showed lower levels of HIF-1α, VEGFR1, and MMP-9 proteins compared to lymph nodes without metastasis, while VEGFR2 protein levels were increased. In agreement, HIF-1α expression was correlated with MMP-9. Cox regression analysis demonstrated that higher HIF-1α and MMP-9 protein expression levels and GA and GG genotypes were associated with poor survival. Our findings show that the C1772T and G1790A polymorphisms of the HIF-1α gene are associated with increased expression of the HIF-1α protein in UADTC. The present data indicate that non-metastatic tissues express higher levels of HIF-1α, VEGFR1, and MMP-9, while in metastatic lymph nodes, VEGFR2 protein expression is elevated. The present study also shows that the HIF-1α G1790A polymorphism and its protein expression have an impact on the prognosis of UADTC patients

Correlação entre sintomas e tempo de evolução do câncer do trato aerodigestivo superior com o estádio inicial e avançado

Muitos dos aspectos clínicos e biológicos da história natural do câncer do trato aerodigestivo superior estão por elucidar, o que no Brasil tem como consequência direta a falha sistemática das campanhas de prevenção e de diagnóstico precoce. OBJETIVO: Analisar os sinais e sintomas apresentados por portadores da doença em estadiamentos iniciais e avançados. Outras variáveis como o tempo de evolução da doença, o estado geral e nutricional foram consideradas. MÉTODO: Estudo de coorte histórica com corte transversal em 895 indivíduos portadores do câncer do trato aerodigestivo superior. RESULTADOS: Os sinais e sintomas encontrados não se correlacionaram de forma estatisticamente significativa com o tempo de evolução da doença nem com a doença em fases iniciais, mas evidenciaram um desenvolvimento rápido da doença. CONCLUSÃO: Os resultados sugerem uma doença de início insidioso nas fases iniciais e de rápida evolução. O tempo longo de evolução - maior que três meses, associou-se às pioras nos estados geral e nutricional dos pacientes