Gene p53 mutations are restricted to poorly differentiated and undifferentiated carcinomas of the thyroid gland.

Abstract

The p53 gene was analyzed in tumor specimens obtained from 52 patients with various types of carcinoma of the thyroid gland by a combined molecular and immunocytochemical approach. The histologic types included 37 well-differentiated papillary and follicular carcinomas, 8 poorly differentiated, and 7 undifferentiated carcinomas. The p53 gene was shown to be unaffected in all differentiated tumors by single-strand conformation polymorphism analysis. However, in two out of eight (25%) of poorly differentiated carcinomas and five out of seven (71%) undifferentiated carcinomas, p53 mutations were identified and subsequently characterized by DNA sequencing. One undifferentiated carcinoma displayed two areas with varying degrees of differentiation. The comparative analysis of the p53 gene, in both the more and the less differentiated area of this tumor, clearly showed that the p53 mutation was confined to the latter component of the tumor specimen. These results indicate that mutations of the p53 gene are associated with the most aggressive histologic types of thyroid tumors, such as the undifferentiated carcinoma and, to a certain extent, the poorly differentiated carcinoma, and that the alterations of this gene represent a late genetic event in human thyroid carcinogenesis. (J. Clin. Invest. 1993.91:1753-1760

Clinicopathological and molecular characterization of nine cases of columnar cell variant of papillary thyroid carcinoma

“…In thyroid neoplasms, defective p53 and loss of expression of the antiapoptotic protein, bcl-2, are more common in poorly differentiated and undifferentiated carcinomas than well-differentiated neoplasms. [70][71][72][73][74][75] In this study, nuclear p53 immunoreactivity was weak in three of five aggressive tumors as well as in all indolent tumors, likely reflecting an intact p53 expression. Interestingly, bcl-2 expression was diminished in the majority of indolent tumors, whereas a strong, cytoplasmic staining was seen in the majority of aggressive tumors.…”

Tolerance of high levels of wild-type p53 in transformed epithelial cells dependent on auto-regulation by mdm-2

“…We suggest that this apparent hypersensitivity of the mdm-2 autoregulatory feedback-loop is at least partly cell-type speci®c, and predict that it will occur in those cell types that give rise to tumours able to tolerate overexpression of wild-type p53. Candidates currently include well-di erentiated thyroid carcinomas (Donghi et al, 1993), testicular cancers (Riou et al, 1995) and a signi®cant proportion of breast cancers (Dunn et al, 1993;Cornelis et al, 1994).…”

An update on molecular biology of thyroid cancers

“…In thyroid tumors, loss of TP53 gene activity is observed at a later stage. p53 loss is generally observed in 15-30% of poorly differentiated carcinomas, in 60-80% of ATCs, and is extremely rare in DTCs (Table 1) [86,[117][118][119][120]. p53 inactivation in thyroid cells has been shown to enhance tumor growth and also causes continuous loss of differentiation.…”