The role of the p53 gene in the malignant transformation of pleomorphic adenomas of the parotid gland.

Pleomorphic adenoma (PA), the most common neoplasm of the parotid gland in adults, undergoes malignant transformation in only two to six percent of cases. In order to determine whether or not the p53 gene is involved in the malignant transformation of PA of the parotid gland, we have analyzed archival specimens from four patients with carcinoma ex-pleomorphic adenoma (CEPA) by immunohistochemistry and sequencing of the amplified DNA. Tissue specimens from each patient contained both the CEPA and the precursor PA. Immunostaining revealed that while all CEPA were p53 positive, only one of the four precursor PA was positive for p53. In this case, DNA was isolated from both the PA and CEPA and exons five through eight were amplified using the polymerase chain reaction. The same p53 mutation (single base substitution) was found in both the PA and the CEPA at codon 248. Adjacent normal tissue contained the wild-type p53 sequence. To our knowledge, this is the first report of the same p53 point mutation in both a PA and the associated CEPA of the parotid. These results strongly suggest a role for p53 gene mutation in the malignant transformation of some PA of the parotid gland.