Interinstitutional variation in predictive value of the ThyroSeq v2 genomic classifier for cytologically indeterminate thyroid nodules Journal Article


Authors: Marcadis, A. R.; Valderrabano, P.; Ho, A. S.; Tepe, J.; Swartzwelder, C. E.; Byrd, S.; Sacks, W. L.; Untch, B. R.; Shaha, A. R.; Xu, B.; Lin, O.; Ghossein, R. A.; Wong, R. J.; Marti, J. L.; Morris, L. G. T.
Article Title: Interinstitutional variation in predictive value of the ThyroSeq v2 genomic classifier for cytologically indeterminate thyroid nodules
Abstract: Background: The ThyroSeq v2 next-generation sequencing assay estimates the probability of malignancy in indeterminate thyroid nodules. Its diagnostic accuracy in different practice settings and patient populations is not well understood. Methods: We analyzed 273 Bethesda III/IV indeterminate thyroid nodules evaluated with ThyroSeq at 4 institutions: 2 comprehensive cancer centers (n = 98 and 102), a multicenter health care system (n = 60), and an academic medical center (n = 13). The positive and negative predictive values of ThyroSeq and distribution of final pathologic diagnoses were analyzed and compared with values predicted by Bayes theorem. Results: Across 4 institutions, the positive predictive value was 35% (22%–43%) and negative predictive value was 93% (88%–100%). Predictive values correlated closely with Bayes theorem estimates (r2 = 0.84), although positive predictive values were lower than expected. RAS mutations were the most common molecular alteration. Among 84 RAS-mutated nodules, malignancy risk was variable (25%, range 10%–37%) and distribution of benign diagnoses differed across institutions (adenoma/hyperplasia 12%–85%, noninvasive follicular thyroid neoplasm with papillary-like nuclear features 5%–46%). Conclusion: In a multi-institutional analysis, ThyroSeq positive predictive values were variable and lower than expected. This is attributable to differences in the prevalence of malignancy and variability in pathologist interpretations of noninvasive tumors. It is important that clinicians understand ThyroSeq performance in their practice setting when evaluating these results. © 2018
Keywords: adult; gene mutation; major clinical study; cancer risk; diagnostic accuracy; sensitivity and specificity; gene overexpression; bayes theorem; genetic variability; gene frequency; cytogenetics; adenoma; hyperplasia; thyroid carcinoma; thyroid nodule; oncogene ras; predictive value; thyroid follicular carcinoma; diagnostic test accuracy study; classifier; next generation sequencing; human; priority journal; article
Journal Title: Surgery
Volume: 165
Issue: 1
ISSN: 0039-6060
Publisher: Elsevier Inc.  
Date Published: 2019-01-01
Start Page: 17
End Page: 23; discussion 23-24
Language: English
DOI: 10.1016/j.surg.2018.04.062
PROVIDER: scopus
PMCID: PMC6289715
PUBMED: 30360906
DOI/URL:
Notes: Surgery -- Export Date: 2 January 2019 -- Article -- CODEN: SURGA C2 - 30360906 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Ronald A Ghossein
    291 Ghossein
  2. Ashok R Shaha
    527 Shaha
  3. Oscar Lin
    229 Lin
  4. Richard J Wong
    223 Wong
  5. Luc Morris
    121 Morris
  6. Brian Untch
    23 Untch
  7. Bin   Xu
    44 Xu
  8. Justin Tepe
    1 Tepe
  9. Serena Byrd
    2 Byrd