Clinical performance of a next-generation sequencing assay (ThyroSeq v2) in the evaluation of indeterminate thyroid nodules

Taye, Aida; Gurciullo, Dillon; Miles, Brett A.; Gupta, Ashita; Owen, Randall P.; Inabnet, William B.; Beyda, Jessica; Marti, Jennifer L.

doi:10.1016/j.surg.2017.07.032

Cited by 54 publications

(62 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thyroseq v2 targeted 14 genes and 42 gene fusion products, with an initial reported sensitivity and specificity of >90% (1,2). Independent validation studies confirmed the high negative predictive value but reported lower positive predictive values (3). The current study reports the development and analytical performance of Thyroseq v3, an expanded 112-gene version of this molecular test (4).…”

Section: Introductionmentioning

confidence: 73%

Thyroseq v3 Molecular Test for Indeterminate Thyroid Nodules Has Improved Sensitivity and Specificity

KuoEric¹,

YehMichael²,

LivhitsMasha³

2018

Clinical Thyroidology

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 73%

Thyroseq v3 Molecular Test for Indeterminate Thyroid Nodules Has Improved Sensitivity and Specificity

KuoEric¹,

YehMichael²,

LivhitsMasha³

2018

Clinical Thyroidology

View full text Add to dashboard Cite

“…Because weak driver mutations are common in indeterminate nodules and have been shown to occur in both benign and malignant nodules, [11][12][13][14][15] we examined the degree to which microRNA test results…”

Section: Tive Mpt Results Over Various Baseline Rates Of Surgery (Supmentioning

confidence: 99%

“…In our study, we examined the impact of reflex microRNA testing not only when nodules lacked mutations but also when nodules had weak driver mutations, given their association with both benign and malignant disease. [11][12][13][14][15] We show that incorporation of microRNA 16 One impediment, we experienced in our study was the unavailability of clinical follow-up records for some patients who underwent observation rather than surgery, which enriched our study cohort for…”

Section: Discussionmentioning

confidence: 96%

“…lence 18. This high probability of cancer-free survival for negative results is consistent with a test that effectively rules out the need for surgery.In our study, we examined the impact of reflex microRNA testing not only when nodules lacked mutations but also when nodules had weak driver mutations, given their association with both benign and malignant disease [11][12][13][14][15]. This high probability of cancer-free survival for negative results is consistent with a test that effectively rules out the need for surgery.In our study, we examined the impact of reflex microRNA testing not only when nodules lacked mutations but also when nodules had weak driver mutations, given their association with both benign and malignant disease [11][12][13][14][15].…”

mentioning

confidence: 84%

“…7-10 RAS mutations, the most common type in thyroid nodules, have been reported to have variable positive and negative predictive value for malignancy, often occurring in benign nodules. [11][12][13][14][15] Furthermore, residual risk of malignancy (5%-25%) is present in patients who lack any detectable mutational change. 16,17 Multiple studies have described the ability of RNA-based risk classifiers to help resolve diagnostic uncertainty in indeterminate thyroid nodules.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Clinical impact of testing for mutations and microRNAs in thyroid nodules

Sistrunk

Shifrin

Frager

et al. 2019

Diagnostic Cytopathology

View full text Add to dashboard Cite

Background We report results of a multicenter clinical experience study examining the likelihood of patients with indeterminate thyroid nodules to undergo surgery or have malignant outcome based on multiplatform combination mutation and microRNA testing (MPT). Methods MPT assessed mutations in BRAF, HRAS, KRAS, NRAS, and PIK3CA genes, PAX8/PPARγ, RET/PTC1, and RET/PTC3 gene rearrangements, and the expression of 10 microRNAs. Baseline clinical information at the time of MPT and clinical follow‐up records were reviewed for 337 patients, of which 80% had negative MPT results. Kaplan Meier analysis for cumulative probability of survival without having a surgical procedure or malignant diagnosis over the course of patient follow‐up was determined for MPT results of 180 patients, among which only 14% had malignancy. Results A negative MPT result in nodules with Bethesda III or IV cytology (2009) conferred a high probability of non‐surgical treatment, with only 11% expected to undergo surgery and a high probability of survival without malignancy (92%) for up to 2 years follow up. A positive MPT result conferred a 57% probability of malignancy and was an independent risk factor for undergoing surgical treatment (Hazard Ratio [HR] 9.2, 95% confidence intervals 5.4‐15.9, P < .0001) and for malignancy (HR 13.4, 95% confidence intervals 4.8‐37.2, P < .0001). For nodules with weak driver mutations, positive microRNA test results supported high risk of cancer while negative results downgraded cancer risk. Conclusion MPT results are predictive of real‐world decisions to surgically treat indeterminate thyroid nodules, with those decisions being appropriately aligned with a patient's risk of malignancy over time.

show abstract

Discriminating Interpatient Variabilities of RAS Gene Variants for Precision Detection of Thyroid Cancer

Fu,

Chazen,

MacMillan

et al. 2024

JAMA Netw Open

View full text Add to dashboard Cite

ImportanceInterpatient variabilities in genomic variants may reflect differences in tumor statuses among individuals.ObjectivesTo delineate interpatient variabilities in RAS variants in thyroid tumors based on the fifth World Health Organization classification of thyroid neoplasms and assess their diagnostic significance in cancer detection among patients with thyroid nodules.Design, Setting, and ParticipantsThis prospective diagnostic study analyzed surgically resected thyroid tumors obtained from February 2016 to April 2022 and residual thyroid fine-needle aspiration (FNA) biopsies obtained from January 2020 to March 2021, at Mount Sinai Hospital, Toronto, Ontario, Canada. Data were analyzed from June 20, 2022, to October 15, 2023.ExposuresQuantitative detection of interpatient disparities of RAS variants (ie, NRAS, HRAS, and KRAS) was performed along with assessment of BRAF V600E and TERT promoter variants (C228T and C250T) by detecting their variant allele fractions (VAFs) using digital polymerase chain reaction assays.Main Outcomes and MeasuresInterpatient differences in RAS, BRAF V600E, and TERT promoter variants were analyzed and compared with surgical histopathologic diagnoses. Malignancy rates, sensitivity, specificity, positive predictive values, and negative predictive values were calculated.ResultsA total of 438 surgically resected thyroid tumor tissues and 249 thyroid nodule FNA biopsies were obtained from 620 patients (470 [75.8%] female; mean [SD] age, 50.7 [15.9] years). Median (IQR) follow-up for patients who underwent FNA biopsy analysis and subsequent resection was 88 (50-156) days. Of 438 tumors, 89 (20.3%) were identified with the presence of RAS variants, including 51 (11.6%) with NRAS, 29 (6.6%) with HRAS, and 9 (2.1%) with KRAS. The interpatient differences in these variants were discriminated at VAF levels ranging from 0.15% to 51.53%. The mean (SD) VAF of RAS variants exhibited no significant differences among benign nodules (39.2% [11.2%]), noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) (25.4% [14.3%]), and malignant neoplasms (33.4% [13.8%]) (P = .28), although their distribution was found in 41.7% of NIFTPs and 50.7% of invasive encapsulated follicular variant papillary thyroid carcinomas (P &lt; .001). RAS variants alone, regardless of a low or high VAF, were significantly associated with neoplasms at low risk of tumor recurrence (60.7% of RAS variants vs 26.9% of samples negative for RAS variants; P &lt; .001). Compared with the sensitivity of 54.2% (95% CI, 48.8%-59.4%) and specificity of 100% (95% CI, 94.8%-100%) for BRAF V600E and TERT promoter variant assays, the inclusion of RAS variants into BRAF and TERT promoter variant assays improved sensitivity to 70.5% (95% CI, 65.4%-75.2%), albeit with a reduction in specificity to 88.8% (95% CI, 79.8%-94.1%) in distinguishing malignant neoplasms from benign and NIFTP tumors. Furthermore, interpatient differences in 5 gene variants (NRAS, HRAS, KRAS, BRAF, and TERT) were discriminated in 54 of 126 indeterminate FNAs (42.9%) and 18 of 76 nondiagnostic FNAs (23.7%), and all tumors with follow-up surgical pathology confirmed malignancy.Conclusions and RelevanceThis diagnostic study delineated interpatient differences in RAS variants present in thyroid tumors with a variety of histopathological diagnoses. Discrimination of interpatient variabilities in RAS in combination with BRAF V600E and TERT promoter variants could facilitate cytology examinations in preoperative precision malignancy diagnosis among patients with thyroid nodules.

show abstract

Clinical performance of a next-generation sequencing assay (ThyroSeq v2) in the evaluation of indeterminate thyroid nodules

Cited by 54 publications

References 22 publications

Thyroseq v3 Molecular Test for Indeterminate Thyroid Nodules Has Improved Sensitivity and Specificity

Thyroseq v3 Molecular Test for Indeterminate Thyroid Nodules Has Improved Sensitivity and Specificity

Clinical impact of testing for mutations and microRNAs in thyroid nodules

Discriminating Interpatient Variabilities of RAS Gene Variants for Precision Detection of Thyroid Cancer

Contact Info

Product

Resources

About