1. ¹INSERM U 694, Angers, France
2. ²Faculté de Médecine, Université d'Angers, France
3. ³Laboratoire de Biochimie, CHU Angers, France
4. ⁴Faculté Paris Ile de France Ouest, Service de Pathologie, Hôpital A Paré, Université Versailles Saint-Quentin en Yvelines, Boulogne, France
5. ⁵Fédération de Pathologie Cellulaire et Tissulaire, CHU Angers, France
6. ⁶Département d'Endocrinologie et de Médecine Interne, CHU Angers, France
7. ⁷INSERM U 533, Nantes, France
8. ⁸Faculté de Médecine, Institut du thorax, Université de Nantes, France

Correspondence: Dr F Savagner, INSERM U 694, Laboratoire de Biochimie, CHU Angers, 4 rue Larrey, Angers 49033, France. E-mail: frsavagner@chu-angers.fr

Received 23 April 2007; Revised 3 September 2007; Accepted 18 September 2007; Published online 29 October 2007.

Abstract

Conventional histology failed to classify part of non-medullary thyroid lesions as either benign or malignant. The group of tumours of uncertain malignancy (T-UM) concerns either atypical follicular adenomas or the recently called 'tumours of uncertain malignant potential'. To refine this classification we analysed microarray data from 93 follicular thyroid tumours: 10 T-UM, 3 follicular carcinomas, 13 papillary thyroid carcinomas and 67 follicular adenomas, compared to 73 control thyroid tissue samples. The diagnosis potential of 16 selected genes was validated by real-time quantitative RT–PCR on 6 additional T-UM. The gene expression profiles in several groups were examined with reference to the mutational status of the RET/PTC, BRAF and RAS genes. A pathological score (histological and immunohistochemical) was estimate for each of the T-UM involved in the study. The correlation between the T-UM gene profiles and the pathological score allowed a separation of the samples in two groups of benign or malignant tumours. Our analysis confirms the heterogeneity of T-UM and highlighted the molecular similarities between some cases and true carcinomas. We demonstrated the ability of few marker genes to serve as diagnosis tools and the need of a T-UM pathological scoring.