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Centrifuged supernatants from FNA provide a liquid biopsy option for clinical next‐generation sequencing of thyroid nodules
Author(s) -
Ye Wenrui,
Hannigan Brette,
Zalles Stephanie,
Mehrotra Meenakshi,
Barkoh Bedia A.,
Williams Michelle D.,
Cabanillas Maria E.,
EdeikenMonroe Beth,
Hu Peter,
Duose Dzifa,
Wistuba Ignacio I.,
Medeiros L. Jeffrey,
Stewart John,
Luthra Rajyalakshmi,
RoyChowdhuri Sinchita
Publication year - 2019
Publication title -
cancer cytopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.29
H-Index - 57
eISSN - 1934-6638
pISSN - 1934-662X
DOI - 10.1002/cncy.22098
Subject(s) - thyroid nodules , medicine , fine needle aspiration , v600e , biopsy , concordance , cdkn2a , thyroid cancer , molecular diagnostics , thyroid , thyroid carcinoma , liquid biopsy , indeterminate , pathology , gene mutation , mutation , malignancy , cancer , gene , bioinformatics , biology , biochemistry , mathematics , pure mathematics
Background Molecular testing is recommended as an adjunct to improve the preoperative diagnosis of fine‐needle aspiration (FNA) of thyroid nodules. Centrifuged supernatants from FNA samples, which are typically discarded, have recently emerged as a novel liquid‐based biopsy for molecular testing. This study evaluates the use of thyroid FNA supernatants for detecting clinically relevant mutations. Methods Supernatants from thyroid FNA samples (n = 156) were evaluated. A 50‐gene next‐generation sequencing (NGS) assay was used, and mutation analysis results from a subset of samples were further compared with those of paired FNA smears and/or cell blocks. Results All 156 samples yielded adequate DNA (median, 135 ng; range, 11‐3180 ng), and 129 of these samples (83%) were successfully sequenced by NGS. The most frequently detected somatic mutations included BRAF and RAS mutations, which were followed by RET , TP53 , PTEN , CDKN2A , and PIK3CA mutations. Eleven of 31 cases with an indeterminate cytologic diagnosis and 9 of 12 cases that were suspicious for malignancy had somatic mutations, including the BRAF V600E mutation, which is highly definitive for papillary thyroid carcinoma (PTC). Seven of the 9 indeterminate and suspicious cases with the BRAF V600E mutation had surgical follow‐up, and they were all confirmed to be PTC. A comparison of the mutation profiles derived from supernatants with those of paired smears and/or cell blocks in a small subset of cases (n = 8) showed 100% concordance. Conclusions This study provides evidence that FNA supernatants can be used as a surrogate for thyroid molecular testing to improve diagnostic accuracy in indeterminate nodules, provide prognostic/predictive information, and improve overall patient management.