p73 expression for human buccal epithelial dysplasia and squamous cell carcinoma: does it correlate with nodal status of carcinoma and is there a relationship with malignant change of epithelial dysplasia?

Abstract

Background: TP73, a p53 homologue gene, shares similar structural sequences with p53. The aim of this study was to investigate the p73 expression for human buccal epithelial dysplasia (ED) and squamous cell carcinoma (SCC).

Methods: Seventy-five samples of human buccal ED, including mild, moderate, and severe ED (25 samples in each category), were analyzed for p73 protein expression by means of immunohistochemistry. Twenty-five samples of human buccal SCCs were analyzed for p73 mRNA expression with reverse transcription-polymerase chain reaction (RT-PCR) and were also analyzed for protein expression with immunohistochemical analysis.

Results: By use of immunohistochemical analysis, nuclear staining of p73 protein was detected in a subset of normal mucosa, buccal ED, and SCC specimens. p73 nuclear staining was noted for the basal cells of normal buccal mucosa. For buccal lesions deriving from mild, moderate, and severe ED, p73 protein was observed in basal and parabasal layers and in more superficial cell layers corresponding to the spinous layer. For well-differentiated carcinomas, p73 immunoreactivity was chiefly observed among the less-differentiated cells in the periphery of carcinomatous clusters, whereas moderately differentiated carcinomas revealed homogeneous staining, involving nearly all of the tumor cells. On RT-PCR, the expression of p73 mRNA from buccal SCC was noted to be compatible with the findings of immunohistochemical analysis. An electrophoretic band with a 180-bp PCR product corresponding to p73 mRNA has been observed. The expression of p73 seemed to be significantly elevated for specimens of buccal ED (protein level) and SCC (protein and mRNA levels) compared with the analogous expression for normal control tissue (Fisher's exact test, p <.001). Also, p73 expression (protein and mRNA levels) correlated significantly with cervical lymph node metastasis for cases of buccal SCC (Fisher's exact test, p <.001). Eight cases of ED (protein level) showing p73 positivity have undergone malignant transformation to develop SCCs in 2 years follow-up, but no statistical significance was established (Fisher's exact test, p >.05).

Conclusions: The data suggest that p73 expression may be (1) associated with the differentiation of oral stratified squamous epithelium, (2) an early event in human oral carcinogenesis, and (3) associated with the nodal status of patients with oral carcinoma and a possible indicator for malignant change of oral ED.