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  • Title: PAX8-PPARgamma rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma.
    Author: Castro P, Rebocho AP, Soares RJ, Magalhães J, Roque L, Trovisco V, Vieira de Castro I, Cardoso-de-Oliveira M, Fonseca E, Soares P, Sobrinho-Simões M.
    Journal: J Clin Endocrinol Metab; 2006 Jan; 91(1):213-20. PubMed ID: 16219715.
    Abstract:
    CONTEXT: The clinicopathological 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-PPARgamma rearrangements, RAS mutations, and RAP-1, RAF-1, and BRAF mutations in a series of 40 FVPTCs as well as in 27 follicular thyroid carcinomas (FTCs) and 12 follicular thyroid adenomas (FTAs). Fluorescence in situ hybridization and RT-PCR were used to detect the PAX8-PPARgamma rearrangement and PCR, single strand confirmational polymorphism, and sequencing for searching the mutations. RESULTS: The frequency of PAX8-PPARgamma rearrangement was similar in FVPTCs (37.5%), FTCs (45.5%), and FTAs (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 BRAF(V600E) mutation of conventional PTCs. No mutations were detected in RAP-1 and RAF-1. In FVPTCs, the PAX8-PPARgamma 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-PPARgamma 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-PPARgamma rearrangement, RAS mutations, and BRAF(K601E) in FVPTCs.
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