Clinical impact of testing for mutations and microRNAs in thyroid nodules

Diagn Cytopathol. 2019 Aug;47(8):758-764. doi: 10.1002/dc.24190. Epub 2019 Apr 23.


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.

Keywords: microRNA classifier; molecular analysis; mutation; patient outcomes; thyroid nodules.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Mutation / genetics*
  • Probability
  • Sensitivity and Specificity
  • Thyroid Nodule / genetics*
  • Young Adult


  • MicroRNAs