Does the 3-gene diagnostic assay accurately distinguish benign from malignant thyroid neoplasms?
ABSTRACT 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.
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.
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.
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.
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ABSTRACT: Thyroid fine-needle aspiration (FNA) samples that feature a follicular-patterned, monotonous Hurthle (oncocytic) cell population cannot be diagnosed reliably. The authors of this report recently identified cyclin D3 overexpression on histologic sections of Hurthle cell carcinoma. In this study, they assessed the diagnostic value of cyclin D3 immunohistochemistry added to routine cytology. Fifty-one FNA samples that were suspicious for Hurtle cell neoplasia and that had histologic follow-up (19 malignant cases) were examined. Cyclin D3 expression levels were evaluated in cell block preparations and were compared with levels of the closely related cyclin D1 protein. Greater than 25% positive cells were used as the cutoff point, as suggested by previous studies. Cyclin D1 and cyclin D3 were highly specific (100% for both) and fairly accurate (75% and 92%, respectively) in distinguishing between benign and malignant oncocytic lesions; the positive predictive value (PPV) for each was 100%. However, both cyclins D1 and D3 had low sensitivity (32% and 79%, respectively) and low negative predictive value (NPV) (71% and 89%, respectively). In contrast, by adopting balanced receiver operating characteristic-derived positive cutoff values, cyclin D1 (>or=6.5%) and cyclin D3 (>or=7.5%) were found to be highly sensitive (100% for both) and accurate (90% and 94%, respectively); and the NPV was 100% for both. In contrast, cyclins D1 and D3 had low specificity (84% and 91%, respectively) and a low PPV (79% and 86%, respectively); however, these values improved in samples that were positive for both cyclins (sensitivity, 100%; specificity, 94%; PPV, 90%; NPV, 100%; and accuracy, 96%). Cyclin D3 increased the suspicion of malignancy in indeterminate oncocytic lesions; its diagnostic performance depended on the cutoff point used and was enhanced further when combined with cyclin D1.Cancer 01/2009; 117(6):522-9. DOI:10.1002/cncy.20050 · 4.90 Impact Factor
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ABSTRACT: Although fine-needle aspiration biopsy (FNA) remains the mainstay of the preoperative workup of thyroid nodules, it does not provide a diagnosis in up to 20% of nodules. This group of indeterminate lesions, including lesions with cellular atypia, suspicious cytology, and demonstrating a follicular pattern, provides one of the greatest challenges to researchers in thyroid cancer today. Over the last 2 decades, considerable work has been done to find molecular markers to resolve this diagnostic dilemma. This article explores some of the markers including galectin-3, HBME-1, BRAF, RET/PTC, PAX8-PPARgamma, hTERT, telomerase, miRNA, and microarray and multigene assays. Although no one marker has proven to be a panacea, several combinations of markers have shown great promise as an adjunct to FNA.Surgical Clinics of North America 10/2009; 89(5):1139-55. DOI:10.1016/j.suc.2009.06.012 · 1.93 Impact Factor
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ABSTRACT: Thyroid cancer is the most common endocrine malignancy; it accounts for approximately 1% of all new case of cancer each year, and its incidence has increased significantly over the last few decades. The majority of thyroid tumors originate from follicular epithelial cells. Among them, papillary (PTC) and follicular carcinomas (FTC) represent the most common forms of differentiated thyroid cancer and account for approximately 80% and 15% of all cases, respectively. Specific genetic lesions are associated to each thyroid tumor histotype: BRAF mutations and RET/PTC and TRK oncogenes have been detected in PTC, whereas FTC is characterized by PAX8/PPARgamma rearrangements and RAS mutations. In this review we summarize studies on the molecular biology of the differentiated thyroid tumors, with particular interest in the associated genetic lesions and their role in thyroid carcinogenesis. We also report recent findings on gene expression and miRNA profiles of PTC and FTC.The quarterly journal of nuclear medicine and molecular imaging: official publication of the Italian Association of Nuclear Medicine (AIMN) [and] the International Association of Radiopharmacology (IAR), [and] Section of the Society of.. 10/2009; 53(5):440-53. · 1.72 Impact Factor