Validation of Genetic Markers for Differential Diagnosis of Thyroid Follicular Neoplasms

Abstract

Introduction: Differential diagnosis of follicular neoplasms is a challenging problem, because fine needle aspirates (FNA) and intraoperative frozen biopsy are rarely helpful for it. These lesions include benign (nodular hyperplasia and follicular or Hurthle cell adenoma) and malignant (follicular or Hurthle cell carcinoma and follicular variant of papillary carcinoma) lesion and the final diagnosis is most often determined after thorough examination of the lesion after resection of involved thyroid lobe. Methods: We validated 14 candidate genes (TERT, TFF3, DDIT3, ARG2, ITM1, C1orf24, PLAB, CCND2, PCSK2, c-Met, EMMPRIN, Adrenomedullin, Autotaxin, and TGF β II receptor) that have been suggested as indicators for differential diagnosis of FN in genome-wide expression profiling studies with quantifying mRNA expression of each gene with RT-PCR and real time RT-PCR in our fresh frozen tissue specimens including 6 normal thyroid tissues, 6 FA and 6 FTC. We also compared levels of mRNA expression of these genes according to the pathologic diagnosis, histologic features and immunohistochemical staining results. Results: The fold changes of TERT, TFF3, DDIT3, ITM1 and C1orf24 gene expression showed statistical significance when compared between three types of tissues and Clorf24 was the only gene whose expression was significantly different between FA and FTA ( P = 0.041 ). The fold change of C1orf24 gene expression showed positive correlation with tumor size, number of capsular invasion and Ki-67 labeling index. The fold change of ARG2 and PLAB gene showed positive correlation with number vascular invasion sites.

Conclusions: Clorf24 was a genetic marker that expressed highly in FTC compared to FA and ARG2 and PLAB were potential markers indicating vascular invasion in FN among 14 molecular markers selected from other genome-wide methods. ------------------------------------- Keywords: Follicular adenoma, Follicular carcinoma, Genetic marker,