The Diagnostic Utility of Combination of HMGA2 and IMP3 qRT-PCR Testing in Thyroid Neoplasms. Issue 1 (January 2015)

• Record Type: Journal Article
• Authors: Jin, Long; Lloyd, Ricardo V.; Henry, Michael R.; Erickson, Lori A.; Sebo, Thomas J.; Rumilla, Kandelaria M.; Zhang, Jun
• Is Part Of: Applied immunohistochemistry & molecular morphology. Volume 23:Issue 1(2015)
• Publication Date: 2015-01
• Subjects: Diagnostic immunohistochemistry -- Periodicals; Immunohistochemistry -- Periodicals; Cells -- Morphology -- Periodicals; Molecular diagnosis -- Periodicals; 616.079
• DOI: 10.1097/PAI.0000000000000031
• Languages: English
• ISSNs: 1541-2016

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <p>The diagnosis of malignant thyroid tumors in some cytologic and histologic specimens remains challenging. High-mobility group A2 (<italic>HMGA2</italic>) expression and insulin-like growth factor II mRNA-binding protein-3 (<italic>IMP3</italic>) expression were evaluated by relative quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The aim of this study was to evaluate whether the combination of <italic>HMGA2</italic> and <italic>IMP3</italic> qRT-PCR was diagnostically useful in differentiating benign from malignant thyroid neoplasms. Fine-needle aspiration (FNA) specimens from 120 patients including 56 benign lesions and 64 carcinomas were used. The available 80 corresponding formalin-fixed paraffin-embedded (FFPE) thyroid tissues from 66 patients were also included in this study. <italic>HMGA2</italic> and <italic>IMP3</italic> expression levels were detected by qRT-PCR and reported as relative fold change after normalizing with a calibrator. The diagnostic utilities of <italic>HMGA2</italic> and <italic>IMP3</italic> qRT-PCR tests were evaluated individually and in combination. In FNA specimens, <italic>HMGA2</italic> and <italic>IMP3</italic> expression was consistently higher in thyroid malignancies compared with benign lesions in all subgroups except in Hürthle cell tumors. After exclusion of Hürthle cell tumors, the sensitivity was 90.2% for <italic>HMGA2</italic>, 88.2% for <italic>IMP3</italic>, and 98% for <italic>HMGA2+IMP3</italic>; the specificity was 97.1% for <italic>HMGA2</italic>, 79.4% for <italic>IMP3</italic>, and 79.4% for <italic>HMGA+IMP3</italic>. qRT-PCR data showed similar results in FFPE tissues: the sensitivity was 84.2% for <italic>HMGA2</italic>, 85.7% for <italic>IMP3</italic>, and 94.7% for <italic>HMGA2+IMP3</italic>; the specificity was 96.9% for <italic>HMGA2</italic>, 91.2% for <italic>IMP3</italic>, and 90.6% for <italic>HMGA2+IMP3</italic>. qRT-PCR data were concordant between FNA and FFPE samples for <italic>HMGA2</italic> (97.4%) and <italic>IMP3</italic> (96.9%). The results indicate that <italic>HMGA2</italic> qRT-PCR with high specificity may be a useful ancillary technique to assist in the classification of difficult thyroid specimens, excluding Hürthle cell tumors. The <italic>HMGA2</italic> and <italic>IMP3</italic> qRT-PCR combination model with increased sensitivity and negative predictive value (96.4%) may be useful in screening thyroid cytology specimens.</p> </sec> </abstract>