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 method (PCR-primer introduced restriction with enrichment of mutant alleles [PCR-PIREMA]). A point mutation of the N-ras oncogene at the codon 61 was detected in 16 of 99 (16.2%) thyroid carcinomas examined by this method. No RAS alteration was detected in the group of 11 medullary thyroid carcinomas, while 3 of 31 (10.0%) papillary carcinomas, 2 of 5 (40%) follicular carcinomas, 8 of 44 (18.2%) poorly differentiated carcinomas, and 3 of 5 (60%) undifferentiated carcinomas showed an activation of N-RAS proto-oncogene. Interestingly, two primary follicular tumors and their corresponding bone metastases, showed N-ras mutations. In the same cases we evaluated the expression of thyroglobulin by immunohistochemical analysis. Although the majority of well-differentiated carcinomas expressed a high level of thyroglobulin, the expression of the same antigen was absent or only occasional weakly positive in 33 of 44 poorly differentiated carcinomas. Interestingly, N-ras mutation was restricted to the group of tumours with low or absent thyroglobulin expression, suggesting that this genetic change is prevalent in less differentiated tumors.
Basolo
F
F
Dipartimento di Oncologia, University of Pisa, Italy. f.basolo@do.med.unipi.it
Pisaturo
F
F
Pollina
L E
LE
Fontanini
G
G
Elisei
R
R
Molinaro
E
E
Iacconi
P
P
Miccoli
P
P
Pacini
F
F
D001859:Bone Neoplasms / Q000556:secondary; D002277:Carcinoma / Q000235:genetics* / Q000473:pathology*; D003062:Codon; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D009693:Nucleic Acid Hybridization; D017354:Point Mutation / Q000235:genetics; D016133:Polymerase Chain Reaction / Q000379:methods; D000090063:Proto-Oncogene Mas; D013954:Thyroglobulin / Q000378:metabolism; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology*
D003062:Codon; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D013954:Thyroglobulin