Does the 3-gene diagnostic assay accurately distinguish benign from malignant thyroid neoplasms?
BACKGROUND
A 3-gene (PCSK2, PLAB, CCND2) assay has been reported to have high accuracy for distinguishing benign from malignant thyroid tumors that are often indeterminate on fine-needle aspiration (FNA) biopsy. The aim of the current study was to determine the diagnostic accuracy of the 3-gene assay in thyroid tissue and in FNA biopsy for distinguishing benign from malignant thyroid neoplasms.


METHODS
The messenger ribonucleic acid (mRNA) expression level of 3 genes (PCSK2, PLAB, CCND2) was analyzed by real-time quantitative reverse transcriptase-polymerase chain reaction in 261 frozen thyroid tissue samples (138 benign and 123 malignant), and prospectively, in 144 clinical thyroid FNA samples. To determine the diagnostic accuracy of the 3-gene assay, the area under the curve (AUC) of the receiver operating characteristic curve for each gene individually and in combination was determined.


RESULTS
PCSK2 and CCND2 mRNA expression levels were found to be significantly different between benign and malignant thyroid tissue samples (P < .0001 and P = .0007, respectively), but PLAB mRNA expression level was not (P = .099). In the thyroid tissue samples, the AUC was 0.67 for PCSK2 and 0.62 for CCND2. In the thyroid FNA samples, PCSK2 and CCND2 were significantly differentially expressed between benign and malignant samples (P = .039 and P = .023, respectively). The AUC was 0.59 for PCSK2 and 0.61 for CCND2.


CONCLUSIONS
Although PCSK2 and CCND2 were significantly differentially expressed between benign and malignant thyroid tumors both in tissue and in FNA samples, the diagnostic accuracy of the 3-gene assay was low. These findings demonstrate that it is essential for studies to validate the diagnostic accuracy and clinical utility of emerging candidate diagnostic thyroid cancer markers if they are to be translated into clinically useful markers for making patient care decisions.
Shibru
Daniel
D
Department of Surgery, University of California at San Francisco, San Francisco, California 94143-1674, USA.
Hwang
Jimmy
J
Khanafshar
Elham
E
Duh
Quan-Yang
QY
Clark
Orlo H
OH
Kebebew
Electron
E
D044963:Biopsy, Fine-Needle; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics; D016207:Cytokines / Q000235:genetics; D015870:Gene Expression; D055436:Growth Differentiation Factor 15; D006801:Humans; D025202:Molecular Diagnostic Techniques; D016133:Polymerase Chain Reaction; D045706:Proprotein Convertase 2 / Q000235:genetics; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*
C080336:CCND2 protein, human; D056742:Cyclin D2; D016213:Cyclins; D016207:Cytokines; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; D045706:Proprotein Convertase 2