[Aspiration biopsy-nucleic acid diagnosis for widely used preparative testing]

Cancer is believed to be generated from normal cells via multi-step carcinogenesis. This hypothesis led researchers to perform studies utilizing genetic alternations in cancer cells in pre or post operative diagnostic tests. However, such an approach has not led to the establishment of widely used molecular-based diagnostic methods, which shows a clear contrast to conventional tumor markers. Although fine needle aspiration biopsy (FNAB) is the most accurate tool for preoperative diagnosis of thyroid malignancy, differential diagnosis between thyroid follicular adenomas and follicular carcinomas is quite difficult. Thus, a preoperative diagnostic method for follicular tumor has been anticipated for a long time. We tried to find a molecular marker to distinguish benign and malignant thyroid nodules based on a gene expression which can be used in Aspiration Biopsy-Nucleic Acid Diagnosis (ABND), and found that the decreased expression of trefoil factor 3 (TFF3) mRNA is a promising marker of thyroid malignancies, including follicular carcinoma. Furthermore, we established a novel method to separate thyroid tumor cells from blood cells using mesh filtration in order to avoid interference with peripheral blood cells that are aspirated simultaneously by FNAB. Using this method, we started a clinical trial and measured TFF3 mRNA in aspirates obtained from patients with a thyroid nodule. All preoperative aspirates diagnosed as malignant by cytology showed a low TFF3 mRNA expression. The preoperative aspirates diagnosed as benign by cytology showed extremely varied TFF3 mRNA expressions and about 20% showed a low TFF3 mRNA expression. Since ABND measuring TFF3 mRNA in aspirates covers the majority of thyroid malignancies and thyroid nodule is a very common clinical problem, it is expected to be the first widely used molecular-based screening test of cancer.