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Submitted on June 16, 2005
Accepted on October 4, 2005
rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma
Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal, Department of Pathology, Medical Faculty of Porto, Porto, Portugal, Centro de Investigação de Patobiologia Molecular, Instituto Português de Oncologia Francisco Gentil, Lisboa, Portugal, Department of Pathology, Medical Faculty, University of São Paulo, São Paulo, Brazil, Department of Surgery, Medical Faculty of Porto, Porto, Portugal
* To whom correspondence should be addressed. E-mail: ssimoes{at}ipatimup.pt.
Context: The clinicopathologic characteristics and the molecular features of the follicular variant of papillary thyroid carcinoma (FVPTC) remain controversial. Objective/Design/Patients: In an attempt to clarify such controversies and to find whether or not FVPTC cases share the molecular features of follicular tumors we searched for the presence of PAX8-PPAR
rearrangements, RAS mutations, and RAP-1, RAF-1 and BRAF mutations in a series of 40 FVPTC, as well as in 27 follicular carcinomas (FTC) and 12 follicular adenomas (FTA). FISH and RT-PCR were used to detect the PAX8-PPAR rearrangement and PCR, SSCP and sequencing for searching the mutations. Results: The frequency of PAX8-PPAR rearrangement was similar in FVPTC (37.5%), FTC (45.5%) and FTA (33.3%). The same holds true regarding the frequency and type of RAS mutations: FVPTC-25.0%, FTC-22.2% and FTA-33.3%. BRAF mutations were only detected in FVPTC (10%); the BRAF mutations in these cases (K601E and G474R) are different from the typical BRAFV600E mutation of conventional PTC. No mutations were detected in RAP-1 and RAF-1. In FVPTC, the PAX8-PPAR rearrangement was significantly associated with multifocality and vascular invasion, whereas the RAS mutations were significantly associated with the large tumor size. There were three cases of FVPTC, three FTCs and one FTA, harboring both PAX8-PPAR rearrangement and RAS mutations; patients with such tumors were usually very young. Conclusions: We conclude that a subset of FVPTC shares some of the molecular features of follicular tumors. Further studies are necessary to clarify the putative clinical significance (e.g. association to blood born metastases) of PAX8-PPAR rearrangement, RAS mutations and BRAK601E in FVPTC.
rearrangement •
RAS mutations •
BRAF mutations
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