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      Role of gene expression profiling in defining indeterminate thyroid nodules in addition to BRAF analysis.

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          Abstract

          Fine-needle aspiration (FNA) is routinely used in the preoperative evaluation of thyroid nodules. However, 15% to 30% of aspirations yield indeterminate cytologic findings. Because the assessment of BRAF mutations seems to improve the diagnostic accuracy, this study evaluated BRAF mutations with Sanger sequencing and real-time methods in 650 consecutive thyroid aspirates. In addition, the expression of a large number of genes involved in basement membrane remodeling, extracellular matrix proteolysis, and cell adhesion was studied in both benign and malignant nodules to identify new diagnostic tools. In this prospective series, despite the use of a very sensitive BRAF mutational testing method, the frequency of a BRAF alteration being identified in indeterminate FNA samples was 3 of 68. Expression analysis revealed several genes that were differentially expressed between benign and malignant nodules (transforming growth factor, cadherin 1, collagen α1, catenin α1, integrin α3, and fibronectin 1 [FN1]), between follicular adenomas and follicular variant of papillary thyroid carcinoma (FN1, laminin γ1, integrin β2, connective tissue growth factor, catenin δ1, and integrin αV), and between BRAF-wild-type and BRAF-mutated papillary thyroid carcinomas (TIMP metallopeptidase inhibitor 1; catenin α1; secreted phosphoprotein 1; FN1; ADAM metallopeptidase with thrombospondin type 1 motif, 1; and selectin L). These data were partially confirmed with real-time polymerase chain reaction analysis and immunohistochemistry. When the cost/benefit ratio of the procedures was taken into account, BRAF mutational testing failed to increase diagnostic accuracy in cytologically indeterminate nodules. However, the additional analysis of the expression of specific molecular markers could have possible utility as a diagnostic tool, although further evidence based on a large series of samples is needed before definitive conclusions can be drawn. Cancer Cytopathol 2016;124:340-9. © 2015 American Cancer Society.

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          Author and article information

          Journal
          Cancer Cytopathol
          Cancer cytopathology
          Wiley
          1934-6638
          1934-662X
          May 2016
          : 124
          : 5
          Affiliations
          [1 ] Unit of Pathological Anatomy, Department of Surgical, Medical, and Molecular Pathology and Critical Care Medicine, University of Pisa, Pisa, Italy.
          [2 ] Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
          [3 ] Section of Cytopathology, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy.
          Article
          10.1002/cncy.21681
          26749005
          d4f82a7b-c163-49e3-affa-dd6fa8c98378
          History

          TIR3,BRAF,cytology,expression analysis,thyroid cancer
          TIR3, BRAF, cytology, expression analysis, thyroid cancer

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