RESUMEN
AIM: The aim of this study was to analyse allelic loss of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) gene and its protein immuno-expression in dysplastic oral lesions and oral squamous cell carcinomas (OSCCs). METHODS AND RESULTS: Samples were collected from 153 patients [20 ranulas used as a control (C); 30 leucoplakias with mild dysplasia (MD); 30 leucoplakias with moderate to severe dysplasia (MSD); 73 oral squamous cell carcinoma (OSCC)]. PTEN protein expression was investigated using immunohistochemistry, and PTEN allelic loss was analysed by fluorescence in-situ hybridisation (FISH). Differences among groups were evaluated using the χ2 test. PTEN expression was higher in MSD (P = 0.002) and OSCC (P = 0.0259) compared with the C group; additionally, a higher expression was observed in MSD (P = 0.0035) and OSCC (P = 0.049) than MD. Regarding FISH analysis, a higher hemizygous (single copy) loss was observed in OSCC than in C (P = 0.0467) and in OSCC than in MD (P = 0.0175), as well as a higher homozygous deletion in OSCC compared with C (P = 0.0159) and OSCC than MD (P = 0.0145). CONCLUSION: The results of this work suggest that PTEN allelic loss is an important mechanism in the late stage of the development of oral potentially malignant lesions into oral cancer.
Asunto(s)
Carcinoma de Células Escamosas/genética , Transformación Celular Neoplásica/genética , Neoplasias de Cabeza y Cuello/genética , Leucoplasia Bucal/genética , Neoplasias de la Boca/genética , Fosfohidrolasa PTEN/genética , Lesiones Precancerosas/genética , Adulto , Anciano , Anciano de 80 o más Años , Alelos , Carcinoma de Células Escamosas/patología , Femenino , Neoplasias de Cabeza y Cuello/patología , Humanos , Leucoplasia Bucal/patología , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/patología , Lesiones Precancerosas/patología , Carcinoma de Células Escamosas de Cabeza y CuelloAsunto(s)
Envejecimiento/genética , Carcinoma Adenoide Quístico/genética , Cromatina/metabolismo , Cisplatino/uso terapéutico , Inhibidores de Histona Desacetilasas/uso terapéutico , Células Madre Neoplásicas/metabolismo , Carcinoma Adenoide Quístico/metabolismo , Cisplatino/farmacología , Humanos , Células Madre Neoplásicas/patologíaRESUMEN
The prediction of tumor behavior for patients with oral carcinomas remains a challenge for clinicians. The presence of lymph node metastasis is the most important prognostic factor but it is limited in predicting local relapse or survival. This highlights the need for identifying biomarkers that may effectively contribute to prediction of recurrence and tumor spread. In this study, we used one- and two-dimensional gel electrophoresis, mass spectrometry and immunodetection methods to analyze protein expression in oral squamous cell carcinomas. Using a refinement for classifying oral carcinomas in regard to prognosis, we analyzed small but lymph node metastasis-positive versus large, lymph node metastasis-negative tumors in order to contribute to the molecular characterization of subgroups with risk of dissemination. Specific protein patterns favoring metastasis were observed in the "more-aggressive" group defined by the present study. This group displayed upregulation of proteins involved in migration, adhesion, angiogenesis, cell cycle regulation, anti-apoptosis and epithelial to mesenchymal transition, whereas the "less-aggressive" group was engaged in keratinocyte differentiation, epidermis development, inflammation and immune response. Besides the identification of several proteins not yet described as deregulated in oral carcinomas, the present study demonstrated for the first time the role of cofilin-1 in modulating cell invasion in oral carcinomas.