Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms.
BACKGROUND
Approximately 30% of fine-needle aspiration (FNA) biopsies of thyroid nodules are indeterminate, nondiagnostic, or suspicious. The purpose of the current study was to determine the accuracy of novel candidate diagnostic markers to distinguish benign from malignant thyroid neoplasms, and to predict the extent of disease.


METHODS
A real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) assay of 6 novel candidate diagnostic and extent of disease marker genes (extracellular matrix protein 1 [ECM1]; transmembrane protease, serine 4 [TMPRSS4]; angiopoietin 2 [ANGPT2]; TIMP metallopeptidase inhibitor 1 [TIMP1]; ephrin-B2 [EFNB2], and epidermal growth factor receptor [EGFR]) was used in 126 thyroid tissues. To evaluate the performance of the scoring model for the diagnostic markers in combination, the area under the receiver operating characteristic (ROC) curve (AUC) was determined.


RESULTS
The levels of ECM1, TMPRSS4, ANGPT2, and TIMP1 mRNA expression were found to be independent diagnostic markers of malignant thyroid neoplasms. The AUC for the 4 diagnostic genes in combination was 0.993 with a sensitivity of 100%, a specificity of 94.6%, a positive predictive value of 96.5%, and a negative predictive value of 100%. In 31 thyroid nodule FNA biopsy samples, the scoring model had a sensitivity of 91.0%, a specificity of 95.0%, a positive predictive value of 92.9%, and a negative predictive value of 92.3%. The multigene assay correctly classified 93% of tumors into the correct risk group (low-risk vs. high-risk) with a sensitivity of 78.9% (true positive in high-risk tumors), specificity of 92% (true negative in low-risk tumors), positive predictive value of 87.5%, and negative predictive value of 92%. In 11 malignant thyroid nodule FNA samples, the extent of disease scoring model correctly identified 3 of 4 high-risk differentiated thyroid cancers and 7 of 7 low-risk differentiated thyroid cancers.


CONCLUSIONS
This novel multigene assay is an excellent diagnostic and extent of disease marker for differentiated thyroid cancer and would be a helpful adjunct to FNA biopsy of thyroid nodules.
Kebebew
Electron
E
Endocrine Surgery and Oncology Program, San Francisco Comprehensive Cancer Center, University of California-San Francisco, San Francisco, California 94143-1674, USA. kebebewe@surgery.ucsf.edu
Peng
Miao
M
Reiff
Emily
E
McMillan
Alex
A