P53 MUTATIONS IN ALL STAGES OF THYROID CARCINOMAS

The p53 gene has been implicated as a tumor suppressor gene whose inac tivation by mutations has been noted in a variety of human malignancie s. Using single strand conformation polymorphism analysis of cDNA frag ments amplified by reverse transcription-polymerase chain reaction, we analyzed 57 thyroid tumor specimens (8 follicular adenomas and 49 car cinomas) 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. Mut ations were found in 1 of 5 anaplastic carcinomas and 11 of 44 differe ntiated carcinomas. Three of these 11 differentiated tumor specimens s howed foci of solid tissue with evidence of dedifferentiation. Two sam ples (1 with anaplastic carcinoma, the other with papillary carcinoma) had double mutations on the same allele resulting in a frameshift. Mo st mutations were point mutations, and 50% of those were G:C to A:T tr ansitions. 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 i n thyroid carcinogenesis and may play an important role in the maligna nt transformation of thyroid cells as well as thyroid tumor progressio n.