Combination of HMGA2 and IMP3 Relative Quantitative RT-PCR Can Improve the Diagnostic Utility in Thyroid Neoplasms
Long Jin, Ricardo V Lloyd, Kandelaria M Rumilla, Jun Zhang. Mayo Clinic, Rochester, MN; University of Wisconsin School of Medicine and Public Health, Madison, WI
Background: The distinction between benign and malignant thyroid tumors in some cytological and histological specimens remains challenging. High Mobility Group A2 (HMGA2) and insulin-like growth factor II mRNA binding protein-3 (IMP3) expression analyzed by relative quantitative RT-PCR (qRT-PCR) have been reported to distinguish benign from malignant thyroid tumors with high sensitivity and specificity. We evaluated the diagnostic utility of HMGA2 and IMP3 expression levels, individually and in combination, in thyroid tumors.
Design: 120 thyroid fine needle aspiration (FNA) specimens (10 hyperplastic, 4 Hashimoto's thyroiditis (HT), 20 follicular adenomas (FA), 22 Hürthle cell adenomas (HA), 24 classical papillary thyroid carcinomas (PTC), 10 follicular variant PTC (FVPTC), 17 follicular thyroid carcinomas (FTC), and 13 Hürthle cell carcinomas (HC)) and 80 corresponding formalin-fixed paraffin-embedded (FFPE) tissues (9 normal thyroids, 11 hyperplastic, 2 HT, 12 FA, 14 HA, 10 PTC, 5 FVPTC, 6 FTC, and 11 HC) were included in this study. HMGA2 and IMP3 qRT-PCR were performed on a LightCycler 480. HMGA2 and IMP3 mRNA levels were expressed as fold change compared to normal thyroid level. The qRT-PCR results were evaluated with HMGA2, IMP3 or HMGA2 + IMP3 (HMGA2 positive and /or IMP3 positive) separately. The test sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were analyzed.
Results: HMGA2 and IMP3 expression in FNAs was consistently higher in thyroid malignancies compared to benign samples in all subgroups except HA and HC. After exclusion of HA and HC, the sensitivity was 90.2% (HMGA2) and 88.2% (IMP3); the specificity was 97.1% (HMGA2) and 79.4% (IMP3). Combining HMGA2 and IMP3 qRT-PCR data generated 98% sensitivity and 96.4% NPV. QRT-PCR data showed similar results in FFPE tissues: sensitivity was 84.2% (HMGA2), 85.7% (IMP3) and 94.7% (HMGA2 + IMP3); specificity was 96.9% (HMGA2), 91.2% (IMP3) and 90.6% (HMGA2 + IMP3). Combining HMGA2 + IMP3 data also increased the sensitivity to 94.7% and NPV to 96.7%. QRT-PCR data were concordant between FNA and FFPE samples for HMGA2 (97.4%) and IMP3 (96.9%).
Conclusions: HMGA2 and IMP3 expression by qRT-PCR analysis may be a useful ancillary technique to assist in the classification of difficult thyroid specimens, excluding Hürthle cell lesions. Combination of HMGA2 and IMP3 qRT-PCR model can increase the sensitivity and NPV and may be especially useful in screening thyroid cytology specimens.
Wednesday, March 6, 2013 1:00 PM
Poster Session VI # 47, Wednesday Afternoon