A preoperative diagnostic test that distinguishes benign from malignant thyroid carcinoma based on gene expression

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 (Pless than or equal to.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.Universidade Federal de São Paulo, Mol Endocrinol Lab, Div Endocrinol, Dept Med, São Paulo, BrazilUniversidade Federal de São Paulo, Div Genet, Dept Morphol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, São Paulo, BrazilDuke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC USAJohns Hopkins Univ, Sch Med, Dept Neurosurg, Baltimore, MD 21205 USAUniversidade Federal de São Paulo, Mol Endocrinol Lab, Div Endocrinol, Dept Med, São Paulo, BrazilUniversidade Federal de São Paulo, Div Genet, Dept Morphol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, São Paulo, BrazilWeb of Scienc