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Paper 18 (1045)
DIAGNOSTIC AND PROGNOSTIC VALUE OF ANGIOGENESIS-MODULATING GENES IN MALIGNANT THYROID NEOPLASMS.
Background: Angiogenesis is an essential biological event in the pathogenesis of all solid human malignancies. We postulated that expression analysis of genes that modulate tumor angiogenesis would identify differentially expressed genes that would help to distinguish benign from malignant thyroid neoplasms.
The 26th Annual Meeting of the American
Association of Endocrine Surgeons
April 3rd- 5th,2005 - Paradisus Riviera Cancun.
Electron Kebebew MD, Miao Peng MD, Quan-Yang Duh MD, Orlo Clark MD, David Ginzinger Ph.D, Emily Reiff BS.
University of California, San Francisco, CA
Methods: A cDNA array with 96 genes known to modulate angiogenesis was used to identify genes differentially expressed (2-fold higher or lower) in malignant versus benign thyroid neoplasms. Quantitative PCR was used to confirm cDNA array expression data in 123 patients (4 normal thyroid, 26 hyperplastic nodules, 27 follicular adenoma, 23 follicular carcinoma, 18 follicular variant of papillary carcinoma, 25 papillary carcinoma). Logistic regression analysis was used to define expression cutoff values and diagnostic accuracy.
Results: We found 22 genes were upregulated in malignant thyroid neoplasms by cDNA array analysis but only 13 genes were significantly higher in malignant than benign thyroid neoplasms by quantitative PCR (p < 0.0383). Of the 13 differentially expressed genes, the combined use of angiopoietin 2 (ANGPT2) and tissue inhibitor of metalloproteinase 1 (TIMP1) mRNA expression levels was best for distinguishing malignant from benign thyroid neoplasms with a sensitivity of 90%, specificity of 85%, positive predictive value of 75%, and negative predictive value of 94%. Measurement of ANGPT2 and TIMP1 mRNA expression levels correctly identified malignant thyroid nodules that were indeterminate on preoperative FNA biopsy in 11 of 14 (78.6%) cases. The level of epidermal growth factor receptor (EGFR) and ephrin B2 (EFNB2) mRNA expression was significantly higher in patients with higher TNM stage tumors or in patients with high risk AMES differentiated thyroid cancer (p < 0.0045).
Conclusions: ANGPT2 and TIMP1 are good diagnostic markers of malignant thyroid nodules and would improve the diagnostic accuracy of FNA biopsy. EGFR and EFNB2 are markers of aggressive differentiated thyroid cancer.