N‐ras mutation of thyroid tumor with special reference to the follicular type

Abstract

Using the method of polymerase chain reaction-single strand conformation polymorphism, the point mutations of the ras oncogenes in a total of 33 thyroid tissues, including 12 follicular adenomas, 6 follicular carcinomas, 11 papillary carcinomas, and 4 undifferentiated carcinomas, were examined. The frequency of the mutation was 3% (1/33) in codon 12, 13 of Ki-ras and 18% (6/33) in codon 61 of N-ras, including 17% (2/12) in follicular adenoma, 50% (3/6) in follicular carcinoma, 0% (0/11) in papillary carcinoma and 25% (1/4) in undifferentiated carcinoma. In follicular adenoma, positivity was observed in microfollicular or trabecular subtypes. Furthermore, the mutation of ras, was examined in histologically different parts, coexisting in the same tumor in a total of four cases. Both the undifferentiated carcinoma and coexisting follicular adenoma, and both the microfollicular adenoma and trabecular nodule growing in the tumor, had the same N-ras (61) mutation. Direct sequencing analysis showed that all mutations were CAA (Gln) to CGA (Arg) transition of codon 61, except for CAA to AAA transversion in one case of follicular carcinoma. A similar genetic abnormality of N-ras genes at codon 61 between follicular adenoma and follicular carcinoma suggests that the mutation of N-ras at codon 61 might play a part in oncogenesis in follicular tumors.

Molecular pathology of well-differentiated thyroid carcinomas

“…In most cases, N-RAS and, less often, H-RAS are mutated in codon 61 (and less often in codons 12 and 13) [23,45]. In some studies, it was advanced that RAS mutations carried a guarded prognosis, but such results have not been confirmed in most series, namely when the analyses were restricted to well-differentiated carcinomas, with the exclusion of poorly differentiated and undifferentiated carcinomas [23,44].…”

Enhanced expression of EGF receptor and low frequency of ras mutations in X-ray-induced rat thyroid tumours

“…In the present study, PCR-SSCP analysis was used for mutation screening [33,45]. This method has also been applied to thyroid tumours in another study [34]. In the above reports [33,34,45] neither false-negative nor false-positive re- Fig.…”

“…This method has also been applied to thyroid tumours in another study [34]. In the above reports [33,34,45] neither false-negative nor false-positive re- Fig. 2a, b Immunohistochemical demonstration of EGFR in rat thyroid tissue.…”

Osteopontin Expression May Be Induced by c-Src in Papillary Thyroid Carcinoma.

“…Several studies indicated a high frequency of ras oncogene activation in thyroid carcinoma including papillary and follicular carcinomas. This ras oncogene mutation is an important event in thyroid tumor progression [20,24,29,30]. On the other hand, mutations of the ras oncogene were also reported in benign thyroid neoplasms [18].…”