Malignant Transformation in Sinonasal Papillomas Is Closely Associated With Aberrant p53 Expression

Background: Sinonasal papillomas are generally benign lesions that arise from the lining of the nasal or paranasal sinuses. Occasionally, however, they may undergo malignant change, an event that is poorly understood. To elucidate the possible molecular basis of this transformation, a series of these lesions were examined for abnormal p53 protein expression and for mutations in the genes of exons 5-8. Methods and Results: Eleven cases of sinonasal papillomas (seven with associated carcinoma) were analyzed immunohistochemically for overexpression of p53 protein, as were three cases of squamous carcinoma. Genetic analysis of exons 5-8 was performed via topographic genotyping of representative tissue and polymerase chain reaction amplification. All seven papillomas with associated carcinoma showed evidence of aberrant function of the p53 gene, as did the three squamous cell carcinomas. Several exhibited point mutations resulting in missense codons. One case possessed a nonsense mutation and was immunonegative. Conclusions: p53 gene mutation appears to be closely associated with malignant transformation in sinonasal papillomas, and genotyping of archival tissues is useful in the evaluation of malignant or potentially malignant lesions.