title: A preoperative diagnostic test that distinguishes benign from malignant thyroid carcinoma based on gene expression.
abstract: Accurate diagnosis of thyroid tumors is challenging. A particular problem is distinguishing between follicular thyroid carcinoma (FTC) and benign follicular thyroid adenoma (FTA), where histology of fine-needle aspirates is not conclusive. It is often necessary to remove healthy thyroid to rule out carcinoma. In order to find markers to improve diagnosis, we quantified gene transcript expression from FTC, FTA, and normal thyroid, revealing 73 differentially expressed transcripts (P < or = 0.0001). Using an independent set of 23 FTCs, FTAs, and matched normal thyroids, 17 genes with large expression differences were tested by real-time RT-PCR. Four genes (DDIT3, ARG2, ITM1, and C1orf24) differed between the two classes FTC and FTA, and a linear combination of expression levels distinguished FTC from FTA with an estimated predictive accuracy of 0.83. Furthermore, immunohistochemistry for DDIT3 and ARG2 showed consistent staining for carcinoma in an independent set 59 follicular tumors (estimated concordance, 0.76; 95% confidence interval, [0.59, 0.93]). A simple test based on a combination of these markers might improve preoperative diagnosis of thyroid nodules, allowing better treatment decisions and reducing long-term health costs.
authors.affiliation: Laboratory of Molecular Endocrinology, Division of Endocrinology, Department of Medicine, Federal University of São Paulo, Brazil.
authors.forename: Janete M
authors.initials: JM
authors.lastname: Cerutti
authors.forename: Rosana
authors.initials: R
authors.lastname: Delcelo
authors.forename: Marcelo João
authors.initials: MJ
authors.lastname: Amadei
authors.forename: Claudia
authors.initials: C
authors.lastname: Nakabashi
authors.forename: Rui M B
authors.initials: RM
authors.lastname: Maciel
authors.forename: Bercedis
authors.initials: B
authors.lastname: Peterson
authors.forename: Jennifer
authors.initials: J
authors.lastname: Shoemaker
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Riggins
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000175:diagnosis*; D000236:Adenoma / Q000175:diagnosis*; D000328:Adult; D000368:Aged; D001707:Biopsy, Needle; D022762:CCAAT-Enhancer-Binding Proteins / Q000032:analysis / Q000235:genetics; D002352:Carrier Proteins / Q000032:analysis; D002648:Child; D005260:Female; D020869:Gene Expression Profiling; D006602:Hexosyltransferases; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D051742:Transcription Factor CHOP; D014157:Transcription Factors / Q000032:analysis / Q000235:genetics
chemical_list: C439569:ABI3BP protein, human; D022762:CCAAT-Enhancer-Binding Proteins; D002352:Carrier Proteins; C497249:DDIT3 protein, human; D008565:Membrane Proteins; D014157:Transcription Factors; D051742:Transcription Factor CHOP; D006602:Hexosyltransferases; C099573:STT3A protein, human