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Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay.
Cancer. 2014 Dec 01; 120(23):3627-34.C

Abstract

BACKGROUND

Fine-needle aspiration (FNA) cytology is a common approach to evaluating thyroid nodules, although 20% to 30% of FNAs have indeterminate cytology, which hampers the appropriate management of these patients. Follicular (or oncocytic) neoplasm/suspicious for a follicular (or oncocytic) neoplasm (FN/SFN) is a common indeterminate diagnosis with a cancer risk of approximately 15% to 30%. In this study, the authors tested whether the most complete next-generation sequencing (NGS) panel of genetic markers could significantly improve cancer diagnosis in these nodules.

METHODS

The evaluation of 143 consecutive FNA samples with a cytologic diagnosis of FN/SFN from patients with known surgical outcomes included 91 retrospective samples and 52 prospective samples. Analyses were performed on a proprietary sequencer using the targeted ThyroSeq v2 NGS panel, which simultaneously tests for point mutations in 13 genes and for 42 types of gene fusions that occur in thyroid cancer. The expression of 8 genes was used to assess the cellular composition of FNA samples.

RESULTS

In the entire cohort, histologic analysis revealed 104 benign nodules and 39 malignant nodules. The most common point mutations involved the neuroblastoma RAS viral oncogene homolog (NRAS), followed by the Kirsten rat sarcoma viral oncogene homolog (KRAS), the telomerase reverse transcriptase (TERT) gene, and the thyroid-stimulating hormone receptor (TSHR) gene. The identified fusions involved the thyroid adenoma associated (THADA) gene; the peroxisome proliferator-activated receptor γ (PPARG) gene; and the neurotrophic tyrosine kinase, receptor, type 3 (NTRK3) gene. Performance characteristics were similar in the retrospective and prospective groups. Among all FN/SFN nodules, preoperative ThyroSeq v2 performed with 90% sensitivity (95% confidence interval [CI], 80%-99%), 93% specificity (95% CI, 88%-98%), a positive predictive value of 83% (95% CI, 72%-95%), a negative predictive value of 96% (95% CI, 92%-100%), and 92% accuracy (95% CI, 88%-97%).

CONCLUSIONS

The current results indicate that comprehensive genotyping of thyroid nodules using a broad NGS panel provides a highly accurate diagnosis for nodules with FN/SFN cytology and should facilitate the optimal management of these patients.

Authors+Show Affiliations

Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25209362

Citation

Nikiforov, Yuri E., et al. "Highly Accurate Diagnosis of Cancer in Thyroid Nodules With Follicular Neoplasm/suspicious for a Follicular Neoplasm Cytology By ThyroSeq V2 Next-generation Sequencing Assay." Cancer, vol. 120, no. 23, 2014, pp. 3627-34.
Nikiforov YE, Carty SE, Chiosea SI, et al. Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. Cancer. 2014;120(23):3627-34.
Nikiforov, Y. E., Carty, S. E., Chiosea, S. I., Coyne, C., Duvvuri, U., Ferris, R. L., Gooding, W. E., Hodak, S. P., LeBeau, S. O., Ohori, N. P., Seethala, R. R., Tublin, M. E., Yip, L., & Nikiforova, M. N. (2014). Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. Cancer, 120(23), 3627-34. https://doi.org/10.1002/cncr.29038
Nikiforov YE, et al. Highly Accurate Diagnosis of Cancer in Thyroid Nodules With Follicular Neoplasm/suspicious for a Follicular Neoplasm Cytology By ThyroSeq V2 Next-generation Sequencing Assay. Cancer. 2014 Dec 1;120(23):3627-34. PubMed PMID: 25209362.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Highly accurate diagnosis of cancer in thyroid nodules with follicular neoplasm/suspicious for a follicular neoplasm cytology by ThyroSeq v2 next-generation sequencing assay. AU - Nikiforov,Yuri E, AU - Carty,Sally E, AU - Chiosea,Simon I, AU - Coyne,Christopher, AU - Duvvuri,Umamaheswar, AU - Ferris,Robert L, AU - Gooding,William E, AU - Hodak,Steven P, AU - LeBeau,Shane O, AU - Ohori,N Paul, AU - Seethala,Raja R, AU - Tublin,Mitchell E, AU - Yip,Linwah, AU - Nikiforova,Marina N, Y1 - 2014/09/10/ PY - 2014/07/24/received PY - 2014/08/18/revised PY - 2014/08/19/accepted PY - 2014/9/12/entrez PY - 2014/9/12/pubmed PY - 2015/1/17/medline KW - cytology KW - genetics KW - molecular diagnosis KW - thyroid cancer KW - thyroid nodules SP - 3627 EP - 34 JF - Cancer JO - Cancer VL - 120 IS - 23 N2 - BACKGROUND: Fine-needle aspiration (FNA) cytology is a common approach to evaluating thyroid nodules, although 20% to 30% of FNAs have indeterminate cytology, which hampers the appropriate management of these patients. Follicular (or oncocytic) neoplasm/suspicious for a follicular (or oncocytic) neoplasm (FN/SFN) is a common indeterminate diagnosis with a cancer risk of approximately 15% to 30%. In this study, the authors tested whether the most complete next-generation sequencing (NGS) panel of genetic markers could significantly improve cancer diagnosis in these nodules. METHODS: The evaluation of 143 consecutive FNA samples with a cytologic diagnosis of FN/SFN from patients with known surgical outcomes included 91 retrospective samples and 52 prospective samples. Analyses were performed on a proprietary sequencer using the targeted ThyroSeq v2 NGS panel, which simultaneously tests for point mutations in 13 genes and for 42 types of gene fusions that occur in thyroid cancer. The expression of 8 genes was used to assess the cellular composition of FNA samples. RESULTS: In the entire cohort, histologic analysis revealed 104 benign nodules and 39 malignant nodules. The most common point mutations involved the neuroblastoma RAS viral oncogene homolog (NRAS), followed by the Kirsten rat sarcoma viral oncogene homolog (KRAS), the telomerase reverse transcriptase (TERT) gene, and the thyroid-stimulating hormone receptor (TSHR) gene. The identified fusions involved the thyroid adenoma associated (THADA) gene; the peroxisome proliferator-activated receptor γ (PPARG) gene; and the neurotrophic tyrosine kinase, receptor, type 3 (NTRK3) gene. Performance characteristics were similar in the retrospective and prospective groups. Among all FN/SFN nodules, preoperative ThyroSeq v2 performed with 90% sensitivity (95% confidence interval [CI], 80%-99%), 93% specificity (95% CI, 88%-98%), a positive predictive value of 83% (95% CI, 72%-95%), a negative predictive value of 96% (95% CI, 92%-100%), and 92% accuracy (95% CI, 88%-97%). CONCLUSIONS: The current results indicate that comprehensive genotyping of thyroid nodules using a broad NGS panel provides a highly accurate diagnosis for nodules with FN/SFN cytology and should facilitate the optimal management of these patients. SN - 1097-0142 UR - https://www.unboundmedicine.com/medline/citation/25209362/Highly_accurate_diagnosis_of_cancer_in_thyroid_nodules_with_follicular_neoplasm/suspicious_for_a_follicular_neoplasm_cytology_by_ThyroSeq_v2_next_generation_sequencing_assay_ L2 - https://doi.org/10.1002/cncr.29038 DB - PRIME DP - Unbound Medicine ER -