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Clinical impact of testing for mutations and microRNAs in thyroid nodules
Author(s) -
Sistrunk John Woody,
Shifrin Alexander,
Frager Marc,
Bardales Ricardo H.,
Thomas Johnson,
Fishman Norman,
Goldberg Philip,
Guttler Richard,
Grant Edward
Publication year - 2019
Publication title -
diagnostic cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.417
H-Index - 65
eISSN - 1097-0339
pISSN - 8755-1039
DOI - 10.1002/dc.24190
Subject(s) - medicine , neuroblastoma ras viral oncogene homolog , kras , hazard ratio , malignancy , thyroid nodules , thyroid cancer , oncology , confidence interval , cancer , gastroenterology , colorectal cancer
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.