P53 GENE MUTATION IN THYROID-CARCINOMA

The pattern of p53 protein expression was examined in 92 cases of thyr oid carcinoma. When the cases were divided into two groups with regard to their cytoplasmic staining only or nucleus staining only, the freq uency of the nucleus staining group was significantly higher in the po orly differentiated carcinoma (PDC) and undifferentiated carcinoma (UD C) 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 fai r prognosis. In this paper, we also elucidate the spectrum of genotypi c 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) of WDC, 17.2% (5/29) of PDC, and 1 6.7% (1/6) of oncocytic carcinoma. Two of five PDC cases and one papil lary 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 cod on 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 nuc leotide changes including two missense and one silent mutation. In con trast to the missense mutations found in PDC, it is interesting to not e that the silent mutation was checked in 28T of well differentiated p apillary carcinoma. These results represents molecular evidence that p 53 gene aberration associated with overexpression of the mutant form o f p53 protein plays a crucial role in the biologically aggressive subt ypes of thyroid carcinoma, and point mutation only was not sufficient to be a prognostic marker for the biologically aggressive malignancy o f 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.