Expression of p63 protein and mRNA in oral epithelial dysplasia

Abstract

Abnormalities in the TP53 are regarded as the most consistent findings in oral squamous cell carcinoma. Two related members of the TP53 family, p73 and p63, have shown remarkable structural similarity to TP53, indicating possible functional and biological interactions. The aim of the present study was to investigate the expression of p63 protein and mRNA in oral epithelial dysplasia. Immunohistochemical p63 staining was compared for samples from 90 male patients with buccal epithelial dysplasias and 15 healthy individuals with normal buccal mucosa and 15 subjects with reactive epithelial hyperplasia of the oral mucosa secondary to traumatic insult. The buccal lesions consisted of mild, moderate and severe epithelial dysplasias (30 samples in each category). The mRNA expression using reverse transcription polymerase chain reaction (RT-PCR) was also included for a subset of available fresh tissue specimens (four samples in each category of mild and moderate epithelial dysplasia; five samples in severe epithelial dysplasia; five samples in each of normal and reactive epithelial hyperplasia). Nuclear p63 staining was demonstrated predominantly in the basal layers of the epithelium of the normal buccal mucosa and reactive epithelial hyperplasia specimens. For epithelial dysplasia lesions, however, staining was not restricted to the basal layers, extending to the middle spinous layer for samples in the mild category, with p63 immunoexpression observed across almost the full thickness of the dysplastic epithelium for analogous moderate and severe specimens. Compared with normal/reactive hyperplastic mucosa, p63 staining in the dysplastic mucosa was significantly increased. The severity of dysplasia was increased with the increase of p63 staining. Furthermore, Delta Np63mRNA was identified in all of the fresh tissue samples whereas expression of transactivation (TA) isotype was not detected. A subset of moderate epithelial dysplasia and severe variant showing p63-positive staining has undergone malignant transformation to squamous cell carcinomas in about 5 years follow-up. Our results indicate that impaired p63 immunoexpression (predominantly Delta N isoform) is associated with the severity of oral epithelial dysplasias and up-regulation of p63 may play a role in the early stage of human oral tumorigenesis.