Does the 3‐gene diagnostic assay accurately distinguish benign from malignant thyroid neoplasms?

Shibru, Daniel; Hwang, Jimmy J.; Khanafshar, Elham; Duh, Quan‐Yang; Clark, Orlo H.; Kebebew, Electron

doi:10.1002/cncr.23703

Cited by 21 publications

(18 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…29 This led to a 3-gene quantitative polymerase chain reaction profiling assay constituted by CCND2, proprotein convertase subtilisin/ kexin type 2 (or PCSK2), and phospholipase (or PLAB) for both tissues and aspirates. 29,30 However, contradictory results were generated. In 1 study, CCND2 was under expressed in malignant samples 29 and up-regulated in the other.…”

Section: Discussionmentioning

confidence: 99%

“…In 1 study, CCND2 was under expressed in malignant samples 29 and up-regulated in the other. 30 Immunohistochemical data were reported only in 1 of the studies. 29 Thus, although current evidence is not sufficiently strong to support the use of cyclin D2 for FNA samples, further investigation is warranted to assess the role of this marker compared with the other D-type cyclins.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Cyclin D1 and D3 overexpression predicts malignant behavior in thyroid fine‐needle aspirates suspicious for Hurthle cell neoplasms

Troncone

Volante

Iaccarino

et al. 2009

Cancer Cytopathology

View full text Add to dashboard Cite

BACKGROUND: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.METHODS: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.RESULTS: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 (≥6.5%) and cyclin D3 (≥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%).CONCLUSIONS: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 (Cancer Cytopathol) 2009. © 2009 American Cancer Society.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cyclin D1 and D3 overexpression predicts malignant behavior in thyroid fine‐needle aspirates suspicious for Hurthle cell neoplasms

Troncone

Volante

Iaccarino

et al. 2009

Cancer Cytopathology

View full text Add to dashboard Cite

show abstract

“…8 in duplicate. To normalized real-time PCR data, we used the method proposed by Shibru et al 8 The Mann-Whitney U test was used to determine differences between mRNA expression levels. A P value of <.05 was considered statistically significant.…”

Section: Real-time Quantitative Reverse Transcriptase Polymerase Chaimentioning

confidence: 99%

“…6 In this setting, the 3-gene mRNA assay, which included cyclin D2 (CCND2), protein convertase 2 (PCSK2), and prostate differentiation factor, allowed molecular classification of follicular carcinoma and follicular adenoma. 7,8 Genes that regulate cell-cycle progression may be differentially expressed in malignant versus benign thyroid nodules.…”

mentioning

confidence: 99%

UbcH10 expression on thyroid fine‐needle aspirates

Guerriero

Ferraro

Desiderio

et al. 2010

Cancer Cytopathology

View full text Add to dashboard Cite

BACKGROUND:Thyroid fine‐needle aspiration (FNA) samples belonging to the follicular neoplasm/suspicious for malignancy classes are controversial. The authors identified UbcH10 as a marker useful in the diagnosis of several neoplasms, including thyroid cancer. Here, analysis of UbcH10 expression by quantitative reverse transcriptase polymerase chain reaction (RT‐PCR) and immunohistochemistry was applied to FNAs.METHODS:A series of 84 follicular neoplasm/suspicious for malignancy FNAs with histological follow‐up (30 malignant) was prospectively collected. UbcH10 immunostaining was performed on cell blocks and compared with that of the proliferation marker Ki‐67. At the mRNA level, UbcH10 was compared with CCND2 and PCSK2 expression, these latter being the best performing components of the previously reported 3‐gene assay; to determine the diagnostic accuracy, the area under the curve (AUC) of the receiver operating characteristic (ROC) curve for each gene individually and in combination was evaluated.RESULTS:UbcH10 and Ki‐67 shared a similar pattern; although UbcH10 expression was higher in malignant than in benign lesions (P < .001), staining was sporadic, and the cutoff value derived by the ROC analysis was too low (1.25%) for routine application. Conversely, UbcH10 expression assessment by quantitative RT‐PCR was effective. UbcH10 mRNA levels associated with malignant histology were significantly higher than those associated with benign histology (P = .02). The AUC was 0.74 for UbcH10, 0.81 for CCDN2, 0.62 for PCSK2, and 0.84 for UbcH10 and CCND2 combination.CONCLUSIONS:UbcH10 quantitative RT‐PCR analysis, rather than immunohistochemistry, is useful to increase the detection of malignancy in thyroid FNAs. UbcH10 may be added as a panel component in quantitative RT‐PCR–based assays. Cancer (Cancer Cytopathol) 2010. © 2010 American Cancer Society.

show abstract

“…The combination of these three genes could differentiate follicular thyroid carcinoma from follicular adenoma with a sensitivity of 100%, and a specificity of 94.7% (34). However, the diagnostic accuracy using these three-genes was found to be low (AUC range between 0.55 and 0.67) when they examined in large number of thyroid tumors and FNA samples representing several histological subtypes (35). The multi-marker assay with four different genes, chromosome 1 open reading frame 24 (C1orf24), integral membrane protein 1 (ITM1), DNA damage-inducible transcript 3 (DDIT3), and arginase II (ARG2) was also studied in thyroid tumors and FNA samples (12,36).…”

mentioning

confidence: 98%

Three-Gene Molecular Diagnostic Model for Thyroid Cancer

Prasad

Kowalski

Tsai

et al. 2012

Thyroid

View full text Add to dashboard Cite

Background: The preoperative diagnosis of thyroid nodules primarily depends upon fine needle aspiration (FNA) cytology. However, up to 25% of FNA samples have associated ''suspicious or indeterminate'', but not diagnostic cytologic reports, resulting in difficulty deciding appropriate clinical management for these patients. We hypothesize that the use of molecular markers as an adjunct to FNA cytology can improve the distinction of benign from malignant nodules that have associated suspicious or indeterminate cytology. Methods: Using microarray analysis, we previously identified and reported on 75 genes useful in the distinction of benign versus malignant thyroid nodules. In the present study, we have further validated the expression of 14 of these markers in a large number of thyroid samples by immunohistochemistry (IHC) analysis of 154 thyroid tumors and quantitative real-time RT-PCR (QRT-PCR) analysis of 95 FNA samples. Of the 154 tumors analyzed by IHC, 44 samples (29%) had associated suspicious or indeterminate FNA cytology. Results: Receiver operating characteristic using three-gene model, (HMGA2, MRC2, and SFN) analysis for the detection of malignant nodules resulted in areas under the curve (AUCs) of ‡ 0.95 (80% sensitivity; 100% specificity) and ‡ 0.84 (71% sensitivity; 84% specificity) for the IHC data in tumors, and QRT-PCR data in FNA samples, respectively. Conclusions: Our results suggest that a three-gene model for the cytological diagnosis of indeterminate thyroid nodules is both feasible and promising. Implementation of this as an adjunct to thyroid cytology may significantly impact the clinical management of patients with suspicious or indeterminate thyroid FNA nodules.

show abstract

Does the 3‐gene diagnostic assay accurately distinguish benign from malignant thyroid neoplasms?

Cited by 21 publications

References 20 publications

Cyclin D1 and D3 overexpression predicts malignant behavior in thyroid fine‐needle aspirates suspicious for Hurthle cell neoplasms

Cyclin D1 and D3 overexpression predicts malignant behavior in thyroid fine‐needle aspirates suspicious for Hurthle cell neoplasms

UbcH10 expression on thyroid fine‐needle aspirates

Three-Gene Molecular Diagnostic Model for Thyroid Cancer

Contact Info

Product

Resources

About