p53 mutations in all stages of thyroid carcinomas

The p53 gene has been implicated as a tumor suppressor gene whose inactivation by mutations has been noted in a variety of human malignancies. Using single strand conformation polymorphism analysis of cDNA fragments amplified by reverse transcription-polymerase chain reaction, we analyzed 57 thyroid tumor specimens (8 follicular adenomas and 49 carcinomas) for the presence of mutations in exons 5, 6, 7, and 8 of p53 gene. Twelve of 49 (24.5%) of the thyroid carcinomas tested presented a mutated p53 allele, but none of the 8 benign thyroid tumors did. Mutations were found in 1 of 5 anaplastic carcinomas and 11 of 44 differentiated carcinomas. Three of these 11 differentiated tumor specimens showed foci of solid tissue with evidence of dedifferentiation. Two samples (1 with anaplastic carcinoma, the other with papillary carcinoma) had double mutations on the same allele resulting in a frameshift. Most mutations were point mutations, and 50% of those were G:C to A:T transitions. Seventy-five percent of the mutations were in exons 7 and 8. The presence of p53 mutations was not associated with tumor stage or histological type. Our data suggest that p53 mutations are involved in thyroid carcinogenesis and may play an important role in the malignant transformation of thyroid cells as well as thyroid tumor progression.