RESUMEN
OBJECTIVE: To determine the usefulness of specific and reliable serum biomarkers to predict cervical lymph node metastasis. METHODS: A cross-sectional study of cases and controls. Thirty-nine serum samples of head and neck squamous cell carcinoma were collected from patients during neoplasm resection. Another 10 serum samples were collected from healthy individuals as a control group. Selected serum biomarkers were E-cadherin, MMP-2, MMP-9, active MMP-13, and p53 autoantibodies. RESULTS: We found a correlation between active MMP-13 (>685 pg/mL; ROC curve analysis 95% CI for sensitivity 79.6-99.3; specificity 49.2-95.1; positive predictive value 65-100; and negative predictive value 36-100) as well as the presence of p53 autoantibodies and lymph node metastasis. Multimarker analysis using MMP-13 and p53 autoantibodies together provided better sensitivity (76%) and specificity (100%). CONCLUSIONS: The combined determination of active MMP-13 and p53 autoantibodies could improve diagnosis of lymphatic metastasis in head and neck squamous cell carcinoma and aid therapeutic decision making.
Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/diagnóstico , Neoplasias de Cabeza y Cuello/diagnóstico , Metaloproteinasa 13 de la Matriz/sangre , Cadherinas/sangre , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/cirugía , Estudios Transversales , Neoplasias de Cabeza y Cuello/sangre , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/cirugía , Humanos , Metástasis Linfática , Metaloproteinasa 2 de la Matriz/sangre , Metaloproteinasa 9 de la Matriz/sangre , Pronóstico , Curva ROC , Sensibilidad y Especificidad , Proteína p53 Supresora de Tumor/inmunologíaRESUMEN
BACKGROUND AND OBJECTIVE: Head and neck squamous cell carcinoma (HNSCC) is a malignant tumor of epithelial origin, which currently represents a major socio-sanitary problem since about 500,000 new cases are reported worldwide every year. In Spain, the HNSCC incidence exceeds 40 cases out of 100.000 individuals/year. HNSCC mortality is closely related to both local relapse and regional or distant lymphatic metastasis. Any reliable tumor-specific biomarker to predict preoperatively HNSCC relapse or lymphatic spread is not currently available. To date, several diagnostic procedures (imaging technologies, biochemical markers) have not shown enough potential to predict the presence of lymph node metastasis. There are new tumor markers related to the metastatic spread that have not been yet evaluated in HNSCC. The main goals of the present study was to determine an specific and reliable serum biomarkers pattern for HNSCC diagnosis, and to predict the HNSCC evolution before surgical therapy by developing appropriate biomarkers related to local relapse and lymphatic metastasis. MATERIAL AND METHOD: Thirty nine serum samples of HNSCC patients were collected during every neoplasm resection. Another 10 serum samples were collected from healthy individuals as a control group. Selected serum biomarkers were: soluble E-cadherine, metalloproteinases (MMP) 2, MMP-9, active MMP-13; and Ac anti-p53. RESULTS: High serum levels of soluble E-cadherine, MMP-9, active MMP-13, and presence Ac anti-p53 were found to be significantly different from those in the control group. There was a statistic association with MMP-2 levels below 290 ng/ml and poor survival. We also found significant differences between active MMP-13 (levels > 685 pg/ml) and the presence of anti-p53 antibodies with the presence of lymph node metastasis. The multimarker analysis using both tumor markers provided the better sensibility (76%) and specifity (100%) values. CONCLUSIONS: The combined determination and valuation of tumor markers could improve the potential diagnosis of lymph node metastasis in HNSCC.