Unique association of p53 mutations with undifferentiated carcinoma of the thyroid

In thyroid there is a wide variety of tumors varying from slowly growing differentiated adenocarcinomas to rapidly proliferating undifferentiated carcinomas. There has been some histopathological evidence that the undifferentiated thyroid carcinomas are derived from differentiated carcinomas. Moreover, it is suspected that some genetic events might be associated with such changes. To identify these genetic events that must be involved in thyroid tumor progression, we initially investigated p53 gene alterations in 10 papillary adenocarcinomas, 4 follicular adenocarcinomas, and 8 undifferentiated carcinomas. Base substitutional mutations in exons 5 to 8 and loss of heterozygosity (LOH) of the p53 gene were not detected in papillary or follicular adenocarcinomas. However, 7 of 8 undifferentiated carcinomasa were carrying base substitutional mutations, and LOH was detected in 3 of 5 informative cases. These results strongly suggest that the mutated p53 gene plays a crucial role in de-differentiation during the progression of thyroid tumors.