RESUMO
The 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.
Assuntos
Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Neoplasias Otorrinolaringológicas/genética , Antígenos CD/metabolismo , Endoglina , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Metástase Linfática , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Otorrinolaringológicas/metabolismo , Neoplasias Otorrinolaringológicas/patologia , Polimorfismo Genético , Prognóstico , Receptores de Superfície Celular/metabolismo , Estudos Retrospectivos , Análise de Sobrevida , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
MEDLINE contains well over 14,000 papers revealed by a search using keywords 'oral squamous cell cancer' or 'oral squamous cell carcinoma', over 27,000 using 'oral carcinoma' and over 48,000 using the keywords 'oral cancer'. It is difficult to see how clinicians could keep abreast of such a subject. This paper attempts to help by providing an overview of the aetiopathogenesis of oral squamous cell carcinoma (OSCC), discussing changes in epidemiology and increasing awareness of the wide range of risk factors, emphasising the genetic background to cancer susceptibility and the genetic changes associated with progression to OSCC and highlighting clinical implications.