HMGA2 gene expression analysis performed on cytologic smears to distinguish benign from malignant thyroid nodules

Up to 80% of thyroid nodules with an indeterminate diagnosis on fine-needle aspiration (FNA) (eg, "suspicious for follicular neoplasm") prove to be benign at the time of surgical resection. Ancillary tests in current use are limited in their ability to improve the preoperative detection of malignant follicular thyroid nodules. Studies using paraffin-embedded tissue have indicated that high mobility group AT-hook 2 (HMGA2) overexpression is present in a high percentage of malignant thyroid neoplasms but not in benign thyroid neoplasms. In the current study, the ability of HMGA2 overexpression analysis to preoperatively distinguish benign from malignant thyroid nodules by reverse transcriptase-polymerase chain reaction (RT-PCR) on suspicious cytologic smears was evaluated.

Patients who underwent thyroid FNA and subsequent thyroid resection from 2001 through 2007 were identified. A subset of these patients who had a cytologic diagnosis of "suspicious" underwent HMGA2 expression analysis. HMGA2 expression was detected on cells scraped from cytologic smears with 1-step, real-time quantitative RT-PCR.

Of the 125 cases identified, RNA extraction and HMGA2 analysis were successful in 115 cases. With an HMGA2 overexpression change of 5.9-fold or greater compared with a thyroid tumor cell line as a positive cutoff, the test was found to have the following overall performance for detecting malignant nodules: sensitivity of 71%, specificity of 97%, positive predictive value of 94%, and negative predictive value of 84%. HMGA2 overexpression was found to have low sensitivity for detecting Hurthle cell carcinoma (33%).

HMGA2 mRNA expression analysis can be performed on cytologic smears and demonstrates a high specificity and positive predictive value and relatively high sensitivity and negative predictive value for detecting malignancy in "suspicious" thyroid aspirate specimens.