Evaluation of ThyroSeq v2 performance in thyroid nodules with indeterminate cytology

Abstract

ThyroSeq v2 claims high positive (PPV) and negative (NPV) predictive values in a wide range of pretest risks of malignancy in indeterminate thyroid nodules (ITNs) (categories B-III and B-IV of the Bethesda system). We evaluated ThyroSeq v2 performance in a cohort of patients with ITNs seen at our Academic Cancer Center from September 2014 to April 2016, in light of the new diagnostic criteria for non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). Our study included 182 patients (76% female) with 190 ITNs consecutively tested with ThyroSeq v2. Patient treatment followed our institutional thyroid nodule clinical pathway. Histologies of nodules with follicular variant papillary thyroid carcinoma or NIFTP diagnoses were reviewed, with reviewers blinded to molecular results. ThyroSeq v2 performance was calculated in nodules with histological confirmation. We identified a mutation in 24% (45) of the nodules. Mutations in were the most prevalent (21), but the positive predictive value of this mutation was much lower (31%) than that in prior reports. In 102 resected ITNs, ThyroSeq v2 performance was as follows: sensitivity 70% (46-88), specificity 77% (66-85), PPV 42% (25-61) and NPV 91% (82-97). The performance in B-IV nodules was significantly better than that in B-III nodules (area under the curve 0.84 vs 0.57, respectively; = 0.03), where it was uninformative. Further studies evaluating ThyroSeq v2 performance are needed, particularly in B-III.

Impact of oncogene panel results on surgical management of cytologically indeterminate thyroid nodules

“…Oncogene panels are generally considered rule‐in tests, although more recent panels like ThyroSeq version 2 (University of Pittsburgh Medical Center, Pittsburgh, PA) also claim rule‐out ability . In our experience, this panel seemed reliable as rule‐out test in follicular neoplasms but not in atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) . Besides the need to bring the performance of oncogene panels into sharper focus, their role in planning the extent of surgery is controversial and needs to be defined .…”

“…A 7‐gene panel that looked for 14 point mutations in 4 genes ( BRAF , HRAS , KRAS , and NRAS ) and 3 rearrangements ( PAX8/PPARG , RET/PTC1 , and RET/PTC3 ), was used in 102 nodules (miRInform; Asuragen, Austin, TX, in 101 of them) until September 2014 . ThyroSeq version 2 that searches for >1000 hotspots in 14 genes ( AKT1 , BRAF , CTNNB1 , GNAS , HRAS , KRAS , NRAS , PIK3CA , PTEN , RET , TP53 , TSHR , TERT , and EIF1AX ) and 42 gene fusions ( ALK , BRAF , IGF2BP3 , NTRK1 , NTRK3 , PPARG , and RET ) was used thereafter in 190 nodules . The change of the panel was based on hypothetical improved performance for our institutional pretest risk of malignancy .…”

Clinical impact of testing for mutations and microRNAs in thyroid nodules

“…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].…”

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

“…ThyroSeq was developed using next-generation sequencing to identify point mutations and gene fusions commonly present in thyroid cancers. 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).…”