TY - JOUR
T1 - Centrifuged supernatants from FNA provide a liquid biopsy option for clinical next-generation sequencing of thyroid nodules
AU - Ye, Wenrui
AU - Hannigan, Brette
AU - Zalles, Stephanie
AU - Mehrotra, Meenakshi
AU - Barkoh, Bedia A.
AU - Williams, Michelle D.
AU - Cabanillas, Maria E.
AU - Edeiken-Monroe, Beth
AU - Hu, Peter
AU - Duose, Dzifa
AU - Wistuba, Ignacio I.
AU - Medeiros, L. Jeffrey
AU - Stewart, John
AU - Luthra, Rajyalakshmi
AU - Roy-Chowdhuri, Sinchita
N1 - Publisher Copyright:
© 2019 American Cancer Society
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
KW - centrifugation
KW - cytopathology
KW - droplet digital polymerase chain reaction
KW - fine-needle aspiration
KW - liquid biopsy
KW - molecular
KW - mutation profiling
KW - next-generation sequencing
KW - supernatant
KW - thyroid
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U2 - 10.1002/cncy.22098
DO - 10.1002/cncy.22098
M3 - Article
C2 - 30620446
AN - SCOPUS:85059695970
SN - 1934-662X
VL - 127
SP - 146
EP - 160
JO - Cancer Cytopathology
JF - Cancer Cytopathology
IS - 3
ER -