8. ECM1 and TMPRRS4 Are Markers Of Malignant Thyroid Nodules and Improve the Accuracy Of Fine Needle Aspiration Biopsy
Electron Kebebew, MD*, Miao Peng, MD*, Quan Y. Duh, MD, Orlo H. Clark, MD, Emily Reiff, BS*, Alex McMillian, PhD
University of California, San Francisco, San Francisco, CA
OBJECTIVE About 15-20% of patients with thyroid nodules have indeterminate fine needle aspiration (FNA) biopsy results and are subjected to "diagnostic" thyroidectomy to exclude a cancer diagnosis. One of the hallmarks of malignant phenotype is cell invasion and metastasis. We hypothesized that genes that regulate cellular invasion/metastasis would be differentially expressed and can serve as diagnostic markers of malignant thyroid nodules.
METHODS cDNA array analysis of 96 extracellular matrix and adhesion molecule genes was used to identify differentially expressed genes (2-fold higher/lower) and confirmed by quantitative PCR.
RESULTS Out of 96 genes, extracellular matrix protein-1 (ECM1) and transmembrane protease serine-4 (TMPRSS4) were significantly higher in malignant (5 anaplastic, 25 follicular, 19 follicular variant of papillary, 26 papillary) than in benign (28 follicular adenoma, 28 hyperplastic nodules) thyroid neoplasms by quantitative PCR (< 0.0002). In 131 patients with benign and malignant thyroid nodules, the combined use of ECM1 and TMPRSS4 mRNA expression had the best accuracy with a sensitivity of 91.2%, specificity of 89.8%, positive predictive value of 85.7%, and negative predictive value of 82.8%. ECM1 and TMPRSS4 expression analysis improved the diagnostic accuracy of FNA biopsy in 36 of 38 indeterminate or suspicious results. By measuring ECM1 and TMPRSS4 mRNA levels, 2 of 6 nodules benign on FNA were correctly identified as malignant, and 11 of 32 nodules malignant on FNA were correctly identified as benign.
CONCLUSIONS ECM1 and TMPRSS4 are excellent diagnostic markers of malignant thyroid nodules and may be used to improve the diagnostic accuracy of FNA biopsy.