title: Can the microRNA signature distinguish between thyroid tumors of uncertain malignant potential and other well-differentiated tumors of the thyroid gland?
abstract: The term 'thyroid tumors of uncertain malignant potential' (TT-UMP) was coined by surgical pathologists to define well-differentiated tumors (WDT) showing inconclusive morphological evidence of malignancy or benignity. We have analyzed the expression of microRNA (miRNA) in a training set of 42 WDT of different histological subtypes: seven follicular tumors of UMP (FT-UMP), six WDT-UMP, seven follicular thyroid adenomas (FTA), 11 conventional papillary thyroid carcinomas (C-PTC), five follicular variants of PTC (FV-PTC), and six follicular thyroid carcinomas (FTC), which led to the identification of about 40 deregulated miRNAs. A subset of these altered miRNAs was independently validated by qRT-PCR, which included 18 supplementary TT-UMP (eight WDT-UMP and ten FT-UMP). Supervised clustering techniques were used to predict the first 42 samples. Based on the four possible outcomes (FTA, C-PTC, FV-PTC, and FTC), about 80% of FTA and C-PTC and 50% of FV-PTC and FTC samples were correctly assigned. Analysis of the independent set of 18 WDT-UMP by quantitative RT-PCR for the selection of the six most discriminating miRNAs was unable to separate FT-UMP from WDT-UMP, suggesting that the miRNA signature is insufficient in characterizing these two clinical entities. We conclude that considering FT-UMP and WDT-UMP as distinct and specific clinical entities may improve the diagnosis of WDT of the thyroid gland. In this context, a small set of miRNAs (i.e. miR-7, miR-146a, miR-146b, miR-200b, miR-221, and miR-222) appears to be useful, though not sufficient per se, in distinguishing TT-UMP from other WDT of the thyroid gland.
authors.affiliation: INSERM ERI-21/EA4319, University of Nice Sophia Antipolis, 06107 Nice, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Lassalle
authors.forename: Véronique
authors.initials: V
authors.lastname: Hofman
authors.forename: Marius
authors.initials: M
authors.lastname: Ilie
authors.forename: Christelle
authors.initials: C
authors.lastname: Bonnetaud
authors.forename: Marie-Pierre
authors.initials: MP
authors.lastname: Puisségur
authors.forename: Patrick
authors.initials: P
authors.lastname: Brest
authors.forename: Céline
authors.initials: C
authors.lastname: Loubatier
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guevara
authors.forename: Olivier
authors.initials: O
authors.lastname: Bordone
authors.forename: Bruno
authors.initials: B
authors.lastname: Cardinaud
authors.forename: Kévin
authors.initials: K
authors.lastname: Lebrigand
authors.forename: Géraldine
authors.initials: G
authors.lastname: Rios
authors.forename: Joseph
authors.initials: J
authors.lastname: Santini
authors.forename: Brigitte
authors.initials: B
authors.lastname: Franc
authors.forename: Bernard
authors.initials: B
authors.lastname: Mari
authors.forename: Abir
authors.initials: A
authors.lastname: Al Ghuzlan
authors.forename: Philippe
authors.initials: P
authors.lastname: Vielh
authors.forename: Pascal
authors.initials: P
authors.lastname: Barbry
authors.forename: Paul
authors.initials: P
authors.lastname: Hofman
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000235:genetics* / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D002454:Cell Differentiation; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D013961:Thyroid Gland / Q000378:metabolism / Q000473:pathology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D035683:MicroRNAs; D012334:RNA, Neoplasm; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf