N-ras mutation in poorly differentiated thyroid carcinomas: Correlation with bone metastases and inverse correlation to thyroglobulin expression

Codon 61 of the N-ras oncogene was screened for mutations in 99 surgically resected thyroid carcinomas by a polymerase chain resection (PCR)-based met hod (PCR-primer introduced restriction with enrichment of mutant alleles [P CR-PIREMA]). A point mutation of the N-ras oncogene at the codon 61 was det ected in 16 of 99 (16.2%) thyroid carcinomas examined by this method. No RA S alteration was detected in the group of 11 medullary thyroid carcinomas, while 3 of 31 (10.0%) papillary carcinomas, 2 of 5 (40%) follicular carcino mas, 8 of 44 (18.2%) poorly differentiated carcinomas, and 3 of 5 (60%) und ifferentiated carcinomas showed an activation of N-RAS proto-oncogene. Inte restingly, two primary follicular tumors and their corresponding bone metas tases, showed N-ras mutations. In the same cases we evaluated the expressio n of thyroglobulin by immunohistochemical analysis. Although the majority o f well-differentiated carcinomas expressed a high level of thyroglobulin, t he expression of the same antigen was absent or only occasional weakly posi tive in 33 of 44 poorly differentiated carcinomas. Interestingly, N-ras mut ation was restricted to the group of tumours with low or absent thyroglobul in expression, suggesting that this genetic change is prevalent in less dif ferentiated tumors.