HMGA2 Gene Expression in Fine-needle Aspiration Samples of Thyroid Nodules as a Marker for Preoperative Diagnosis of Thyroid Cancer

Abstract

There is a great interest in molecular markers that would help in the preoperative diagnosis of malignant thyroid nodules in cases of indeterminate fine-needle aspiration cytology. The aim of this study was to determine the diagnostic accuracy of HMGA2 gene expression in discriminating benign from malignant thyroid nodules. In this study, 237 preoperative thyroid fine-needle aspiration samples were analyzed prospectively for the expression of the HMGA2 gene by real-time reverse transcription polymerase chain reaction. The results were evaluated against the postoperative histopathologic diagnosis or definitive cytologic diagnosis in cases of nodular goiter and Hashimoto thyroiditis. Among 237 samples from patients with thyroid nodules that were analyzed, 231 were adequate for real-time reverse transcription polymerase chain reaction analysis. With a cutoff value of 8.71 for relative gene expression, HMGA2 was positive in 19 (16.4%) of 116 nodular goiter, 1 (2.6%) of 39 Hashimoto thyroiditis, 9 (28.1%) of 32 follicular adenoma, 0 (0%) of 5 Hurthle cell adenoma, 32 (88.9%) of 36 papillary carcinoma, and 3 (100%) of 3 follicular carcinoma samples. In discriminating between malignant and benign thyroid nodules, HMGA2 has shown specificity of 84.5%, sensitivity of 91.9%, positive predictive value of 53.1%, and negative predictive value of 98.2%. High sensitivity and negative predictive value of HMGA2 for preoperative detection of malignant thyroid nodules shown in this study indicate that it may have a role as an ancillary marker in cytology in the management of patients with thyroid nodules.

Diagnostic performance of HMGA2 gene expression for differentiation of malignant thyroid nodules: A systematic review and meta‐analysis

“…Remaining 9 full‐text articles were assessed for eligibility, and 2 articles were excluded due to insufficient data for the calculation of sensitivity and specificity of HMGA2 gene expression in patients with thyroid nodules. Finally, 7 studies (10 results) were selected and were eligible for the systematic review and meta‐analysis and no additional studies were found screening the references of these articles . The characteristics of the included studies are presented in Table .…”

“…Of all 7 studies, 6 studies enrolled patients retrospectively . Two studies used formalin‐fixed paraffin‐embedded (FFPE) thyroid tissue for HMGA2 gene expression scan, and 2 studies used fine‐needle aspiration biopsy (FNAB) samples of thyroid tissue. Other 3 studies used both of FFPE and FNAB samples of thyroid tissue .…”

“…It has been reported that HMGA proteins were highly up‐regulated in several malignancies including thyroid cancers. Therefore, HMGA gene expression has been proposed as an ancillary marker in discriminating between benign and malignant thyroid nodules . In 1995, Chiappetta et al reported that HMGI and HMGY proteins were expressed in human thyroid carcinomas and thyroid carcinoma cell lines, but not in adenomas, goitres, normal thyroid tissues and cells.…”

“…In 1995, Chiappetta et al reported that HMGI and HMGY proteins were expressed in human thyroid carcinomas and thyroid carcinoma cell lines, but not in adenomas, goitres, normal thyroid tissues and cells. Recently, some studies demonstrated high sensitivity and high specificity of HMGA2 expression for discrimination of malignant thyroid nodules . In contrast, other studies reported low sensitivity and low specificity .…”

“…Previously, several studies reported that HMGA expression was associated with thyroid malignancy and the investigators were able to distinguish between benign and malignant thyroid nodules. However, HMGA expression has a wide range of sensitivity and specificity for differentiation of malignant thyroid nodules …”