p53 gene mutation in thyroid carcinoma.

Abstract

The pattern of p53 protein expression was examined in 92 cases of thyroid carcinoma. When the cases were divided into two groups with regard to their cytoplasmic staining only or nucleus staining only, the frequency of the nucleus staining group was significantly higher in the poorly differentiated carcinoma (PDC) and undifferentiated carcinoma (UDC) groups (10.5% and 25%) compared with the other groups of histologic subtype (0%). The results suggest positivity in nucleus staining for p53 may be a marker for the biologically worse carcinomas, PDC and UDC, however, tumors showing only cytoplasmic staining of p53 favor a fair prognosis. In this paper, we also elucidate the spectrum of genotypic aberrations of p53 in each histological subtype. Of 92 thyroid tumor samples analyzed, the overall frequency of p53 mutation was 8.5%. The mutations occurred in 4.35% (2/46) ot WDC, 17.2% (5/29) of PDC, and 16.7% (1/6) of oncocytic carcinoma. Two of five PDC cases and one papillary carcinoma revealed point mutations in exon 8 as follows; GTG (val) to CTG (leu) at codon 272 in case 23T, CGA (arg) to CCA (pro) at codon 306 in case of 30T, and CGG (arg) to AGG (arg) at codon 282 in case 28T. All of the p53 mutations detected were represented by single nucleotide changes including two missense and one silent mutation. In contrast to the missense mutations found in PDC, it is interesting to note that the silent mutation was checked in 28T of well differentiated papillary carcinoma. These results represents molecular evidence that p53 gene aberration associated with overexpression of the mutant form of p53 protein plays a crucial role in the biologically aggressive subtypes of thyroid carcinoma, and point mutation only was not sufficient to be a prognostic marker for the biologically aggressive malignancy of thyroid tumors. There was no p53 gene aberration found in four cases of undifferentiated carcinoma (UDC) studied. The results suggest that other unknown factors should be responsible for the aggressiveness in some UDC of thyroid carcinoma except overexpression of p53.