RESUMO
Oral leukoplakia is the most prevalent and potentially malignant disorder of the oral mucosa. Previous studies have demonstrated that molecular changes of the WWOX gene (WW-domain containing oxidoreductase), a candidate tumor suppressor gene located at 16q23.3-24.1 that spans FRA16D, the second most common fragile site, are present in several malignant neoplasias, including oral squamous cell carcinoma. In this report, the role of the WWOX gene was investigated in 23 cases of oral leukoplakias. Using nested RT-PCR and immunohistochemistry, altered mRNA transcription and/or reduced Wwox protein expression was observed in 35% of the lesions when compared with normal mucosa. The majority of lesions (4/6) with altered transcripts had a reduction in the expression of Wwox protein. Although normal WWOX expression was found in some lesions with dysplasia, all lesions with WWOX mRNA and/or protein expression showed histological evidence of dysplasia and none of the cases without dysplasia presented this alteration. These results show that the WWOX gene alteration is an early genetic alteration and may contribute to oral carcinogenesis.
Assuntos
Genes Supressores de Tumor , Leucoplasia Oral/genética , Oxirredutases/genética , Proteínas Supressoras de Tumor/genética , Adulto , Idoso , Estudos de Casos e Controles , Sítios Frágeis do Cromossomo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Leucoplasia Oral/metabolismo , Leucoplasia Oral/patologia , Masculino , Pessoa de Meia-Idade , Oxirredutases/metabolismo , RNA Mensageiro/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Tabagismo/genética , Tabagismo/patologia , Proteínas Supressoras de Tumor/metabolismo , Oxidorredutase com Domínios WWRESUMO
BACKGROUND: Nasopharyngeal angiofibroma (also known as juvenile nasopharyngeal angiofibroma) is a rare fibroblastic tumor with a vascular component that occurs in the nasopharynx and posterolateral nasal wall of adolescent boys. The etiology of nasopharyngeal angiofibroma remains elusive. This investigation was undertaken to determine if human herpes simplex virus-8 and Epstein-Barr virus are possible etiologic viruses and to determine if they have any association with the age of the patient and/or the proliferative state of the lesion. MATERIALS AND METHODS: Formalin fixed, routinely processed, and paraffin embedded surgical specimens of 15 angiofibromas were submitted to PCR for EBV and HHV-8, while in situ hybridization was also employed for EBV. Immunohistochemical analysis for ki-67 was performed using MIB immunostaining. RESULTS: None of the tumors were positive for HHV-8. The PCR technique produced a false positive reaction in five cases, with all cases non-reactive with EBV-ISH. The age of the patients did not show correlation with the Ki-67 labeling index. CONCLUSION: Angiofibroma does not appear to be associated with either HHV-8 or EBV, thereby excluding these viruses as potential etiologic agents. The lack of a correlation between the proliferative index and the age of the patient suggests the proposed puberty induced, testosterone-dependent tumor growth may not play a significant role in tumor development.