title: Microarray analysis refines classification of non-medullary thyroid tumours of uncertain malignancy.
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.
authors.affiliation: INSERM U 694, Angers, France. frsavagner@chu-angers.fr
authors.forename: J-F
authors.initials: JF
authors.lastname: Fontaine
authors.forename: D
authors.initials: D
authors.lastname: Mirebeau-Prunier
authors.forename: B
authors.initials: B
authors.lastname: Franc
authors.forename: S
authors.initials: S
authors.lastname: Triau
authors.forename: P
authors.initials: P
authors.lastname: Rodien
authors.forename: R
authors.initials: R
authors.lastname: Houlgatte
authors.forename: Y
authors.initials: Y
authors.lastname: Malthièry
authors.forename: F
authors.initials: F
authors.lastname: Savagner
mesh_terms: D002277:Carcinoma / Q000145:classification* / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000145:classification / Q000235:genetics; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D013964:Thyroid Neoplasms / Q000145:classification* / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D016606:Thyroid Nodule / Q000145:classification / Q000175:diagnosis / Q000235:genetics / Q000473:pathology