Evidence that one subset of anaplastic thyroid carcinomas are derived from papillary carcinomas due to BRAF and p53 mutations
Article first published online: 3 MAY 2005
Copyright © 2005 American Cancer Society
Volume 103, Issue 11, pages 2261–2268, 1 June 2005
How to Cite
Quiros, R. M., Ding, H. G., Gattuso, P., Prinz, R. A. and Xu, X. (2005), Evidence that one subset of anaplastic thyroid carcinomas are derived from papillary carcinomas due to BRAF and p53 mutations. Cancer, 103: 2261–2268. doi: 10.1002/cncr.21073
- Issue published online: 18 MAY 2005
- Article first published online: 3 MAY 2005
- Manuscript Revised: 2 FEB 2005
- Manuscript Accepted: 2 FEB 2005
- Manuscript Received: 28 MAY 2004
- Thyroid Research Advisory Council
- ThyCa Foundation
- Department of General Surgery at Rush University Medical Center
- anaplastic thyroid carcinoma;
Anaplastic thyroid carcinoma (ATC) is the most lethal form of thyroid neoplasia and represents the end stage of thyroid tumor progression. In the current study, genetic alterations in a panel of ATC were profiled to determine the origins of ATC.
Eight ATC were analyzed for BRAF mutation at codon 599 by using mutant-allele-specific polymerase chain reaction (PCR) and DNA sequencing of the PCR-amplified exon 15. RAS mutation (HRAS, KRAS, and NRAS) at codons 12, 13, and 61 was analyzed by direct sequencing of PCR-amplified exons 1 and 2 of the RAS gene. RET/PTC rearrangements and p53 mutation were monitored by immunohistochemical (IHC) staining by anti-RET antibodies and an anti-p53 mAb, respectively.
BRAF was mutated in 5 of the 8 ATCs tested. Histologic examination revealed that 4 of these 5 BRAF-mutated ATCs contained a PTC component, suggesting that they may be derived from BRAF-mutated PTC. Of the 3 ATCs with wild-type BRAF, 2 had spindle cell features; one had follicular neoplastic characteristics mixed with papillary structures. Analysis of RAS mutation revealed only an HRAS mutation at codon 11, due to the transversion of GCC to TCC in one ATC with wild-type BRAF. This leads to the substitution of valine to serine. IHC analysis of RET/PTC rearrangements revealed no positive staining of RET in any of 8 ATCs, suggesting that these ATCs are not derived from RET/PTC- rearranged PTC. In contrast, IHC analysis of p53 mutation revealed that p53 was detected in the nuclei of 5 of 5 BRAF-mutated ATCs and 2 of 3 ATCs with wild-type BRAF. p53 staining was present only in anaplastic thyroid tumor cells but not in neighboring papillary thyroid tumor cells.
These results suggest that many ATCs with papillary components are derived from BRAF-mutated PTC, because of the addition of p53 mutation. Cancer 2005. © 2005 American Cancer Society.