Tumor suppressor in oral carcinogenesis

Introduction: The biology and regulation of p73, a p53 homologue is complex, since the gene incorporates both tumor-suppressive and protooncogenic functions. However, the p73 gene is rarely mutated in tumors. A better understanding of p73 pathway is mandatory for the improvement of oral cancer diagnosis and treatment. Aim: The aim of the present study was to evaluate p73 expression in oral potentially malignant disorders compared to oral squamous cell carcinoma. Methods & Materials: p73 expression was assessed in 30 oral squamous cell carcinoma, 30 oral potentially malignant disorders & 10 normal oral mucosa. The immunohistochemistry was carried out by using rabbit anti-human antibody against p73. Results: The Kruskal-Wallis test showed significant increase in p73 expression from normal oral mucosa to potentially malignant disorders to oral squamous cell carcinoma (p=0.00). Using Mann-Whitney test, the p73 expression was significantly higher in severe dysplasias than moderate and mild dysplasias (p=0.00). Similarly, the p73 expression was significantly higher in poorly differentiated squamous cell carcinomas than moderately and well differentiated squamous cell carcinomas (p=0.00). However, p73 expression was statistically insignificant (p=0.853) between severe dysplasia and well differentiated squamous cell carcinomas. Conclusion: The results suggest that p73 acts as a tumor suppressor gene in oral carcinogenesis. From this evidence, it is likely that p73 protein isoforms are instrumental for the maintenance of head & neck squamous epithelial stem cells and progenitors. Conversely, loss of p73 expression is associated with keratinocyte differentiation. Therefore, it is proposed that p73 probably plays a role in the maintenance of stem and progenitor cells, leading to the control of early epithelial differentiation stages.