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S Durand, UMR 664 Inserm, Institut National de la Sante et de la Recherche Medicale, Lyon, France
C Ferraro-Peyret, UMR 664 Inserm, Institut National de la Sante et de la Recherche Medicale, Lyon, France
M Joufre, Unite fonctionnelle de Biologie Cellulaire, Hospices Civils de Lyon, Hopital Edouard-Herriot, Lyon, France
A Chave, Unite fonctionnelle de Biologie Cellulaire, Hospices Civils de Lyon, Hopital Edouard-Herriot, Lyon, France
F Borson-Chazot, UMR 664 Inserm, Institut National de la Sante et de la Recherche Medicale, Lyon, France
S Selmi-Ruby, UMR 664 Inserm, Institut National de la Sante et de la Recherche Medicale, Lyon, France
B Rousset, UMR 664 Inserm, Institut National de la Sante et de la Recherche Medicale, Lyon, France

Correspondence: Bernard Rousset, Email: rousset{at}sante.univ-lyon1.fr

Abstract

About 60-70% of papillary thyroid carcinomas (PTC) present a BRAFT1799A gene mutation or a rearrangement of RET gene (RET/PTC). In this study, we examined whether PTC without BRAFT1799A 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 corresponded to PTC-ga(-) whereas 84% of PTC of classical form were PTC-ga(+). In conclusion, we show that PTC without BRAFT1799A 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.