RESUMO
BACKGROUND/AIMS: Squamous cell carcinoma of the head and neck (HNSCC) is the 6th most common malignancy worldwide with a 5-year survival that has not improved over the last 20-25 years. Factors of prognostic significance for this tumour type include the presence of regional lymph node metastasis and amplification of chromosome 3q21-29, where the p63 gene is located. This gene encodes 6 proteins and is crucial for formation of the oral mucosa, teeth, salivary glands and skin. Each of the 6 different p63 proteins has different characteristics and functions, where some resemble the tumour suppressor protein p53, whilst others have functions that oppose p53. METHODS: To understand the function and importance of p63 in oral mucosa and tumour development we have studied protein as well as mRNA expression in normal oral mucosa and tumours. RESULTS/CONCLUSION: Expression of p63 proteins differs between the cell layers in normal oral mucosa, and primary HNSCC has a high expression level of p63 isoforms normally expressed in basal cells. Data suggest that p63 expression in HNSCC influences tumour cell differentiation.
Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Proteína Supressora de Tumor p53/metabolismo , Biópsia por Agulha , Carcinoma de Células Escamosas/mortalidade , Estudos de Casos e Controles , DNA de Neoplasias/análise , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Imuno-Histoquímica , Masculino , Mucosa Bucal/patologia , Prognóstico , Valores de Referência , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Medição de Risco , Estudos de Amostragem , Sensibilidade e Especificidade , Taxa de Sobrevida , Proteína Supressora de Tumor p53/genéticaRESUMO
The human p63 gene encodes a series of protein isoforms that differ in their N- and/or C-terminal sequences and possess widely varying activities in promoting or repressing p53-related functions and in regulating the proliferation and differentiation of epithelial cells. To gain further information on the role of p63 expression in human tumours, we used quantitative real-time RT-PCR to study individual p63 isoforms in squamous cell carcinomas of the head and neck (SCCHN). In keeping with previous reports, expression of the deltaN- and p63alpha-isoforms predominated and deltaNp63 mRNA was expressed at significantly higher levels in tumours compared to matched normal tissues. Some tumours also expressed the highly efficient transactivator TA- and p63beta-isoforms, and p63beta was significantly increased in tumours compared to matched normal tissue. We could not identify any correlations between different p63-isoform expression patterns and proliferation, p53 status, or telomerase expression. All p63 isoforms could be identified in normal surface epithelium, and micro-dissection showed that the high levels present in basal layers were similar to those seen in tumour tissues. Thus, high-level expression of deltaNp63 in tumour cells may represent maintained expression by the basal cells from which the tumour arose, rather than representing a true over-expression of p63 during tumourigenesis. Tobacco usage, a genotoxic predisposing factor for SCCHN, had no effect on p63 expression in oral epithelium. Taken together, our data indicate that SCCHN maintain expression of high levels of deltaNp63alpha in combination with varying levels of other p63 isoforms, some of which are highly efficient transcriptional activators. The complexity of these p63 expression patterns seen in primary SCCHN indicates that p63 has multifaceted roles in tumour biology.
