DNA ANALYSIS AT P53 LOCUS IN CARCINOMAS ARISING FROM PLEOMORPHIC ADENOMAS OF SALIVARY-GLANDS - COMPARISON OF MOLECULAR STUDY AND P53 IMMUNOSTAINING

Where and how frequently p53 abnormalities are involved in the develop ment of pleomorphic adenoma (PA) and its malignant progression to carc inoma was investigated. The presence of p53 gene abnormalities was ana lyzed in eight patients with carcinoma in pleomorphic adenoma (CPA) by polymerase chain reaction (PCR)-based assays and immunohistochemistry . Normal salivary gland tissue, adenomatous, transitional and carcinom atous areas were microdissected from archival microslides and analyzed for allelic deletions of the p53 gene using two microsatellite marker s at the p53 locus; dinucleotide (CA)(n) repeat and pentanucleotide (A AAAT)(n) repeat. Loss of heterozygosity (LOH) of the p53 gene was dete cted in 57% of adenomas, 86% of transitional lesions and 86% of carcin omas. In contrast, overexpression of p53 oncoprotein was noted immunoh istochemically in 13% of adenomas, 50% of transitional areas and 75% o f carcinomas. All of the tumors with immunoreactivity for p53 oncoprot ein demonstrated LOH, Moreover, when LOH was present in adenomatous or transitional areas, the identical LOH was always detected in the corr esponding carcinomatous areas in the same CPA tumors. These findings i ndicate that p53 gene mutation is an early event and occurs frequently at an early stage of precancerous lesions and may be responsible for most cases of malignant transformation of PA.