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¹ Institut National de la Santé et de la Recherche Médicale, UMR 664, Lyon F-69372, France
² Université Lyon 1, Faculté de Médicine Laennec, Lyon F-69372, France
³ Unité Fonctionnelle de Biologie Cellulaire, Hospices Civils de Lyon, Hôpital Edouard-Herriot, Lyon F-69437, France

(Correspondence should be addressed to B Rousset; Email: rousset{at}sante.univ-lyon1.fr)

About 60–70% of papillary thyroid carcinomas (PTC) present a BRAF^T1799A gene mutation or a rearrangement of RET gene (RET/PTC). In this study, we examined whether PTC without BRAF^T1799A mutation and without RET/PTC rearrangement named PTC-ga(–) were distinguishable from PTC-ga(+) (with one or the other gene alteration) on the basis of gene expression characteristics. We analyzed the mutational state of 116 PTC and we compared gene expression profiles of PTC-ga(+) and PTC-ga(–) from data of a 200 gene macroarray and quantitative PCR. Seventy five PTC were PTC-ga(+) and 41 were PTC-ga(–). Unsupervised analyses of macroarray data by hierarchical clustering led to a complete segregation of PTC-ga(+) and PTC-ga(–). In a series of 42 genes previously recognized as PTC ‘marker’ genes, 22 were found to be expressed at a comparable level in PTC-ga(–) and normal tissue. Thyroid-specific genes, TPO, TG, DIO1, and DIO2 were under-expressed in PTC-ga(+) but expressed at a normal level in PTC-ga(–). A few genes including DUOX1 and DUOX2 were selectively dys-regulated in PTC-ga(–). Tumor grade of PTC-ga(–) was lower than that of PTC-ga(+). There was a strong association between the mutational state and histiotype of PTC; 81% of PTC follicular variants were corresponded to PTC-ga(–), whereas 84% of PTC of classical form were PTC-ga(+). In conclusion, we show that PTC without BRAF^T1799A mutation or RET/PTC rearrangement, mainly corresponding to follicular variants, maintain a thyroid differentiation expression level close to that of normal tissue and should be of better prognosis than PTC with one or the other gene alteration.