Next-generation sequencing of residual cytologic fixative preserved DNA from pancreatic lesions: A pilot study.
Adult
Aged
Aged, 80 and over
Biomarkers, Tumor
/ genetics
Carcinoma, Pancreatic Ductal
/ diagnosis
Cytological Techniques
Endoscopic Ultrasound-Guided Fine Needle Aspiration
Female
High-Throughput Nucleotide Sequencing
/ methods
Humans
Male
Middle Aged
Mutation
Neuroendocrine Tumors
/ diagnosis
Pancreatic Cyst
/ diagnosis
Pancreatic Neoplasms
/ diagnosis
Pilot Projects
Prognosis
Specimen Handling
Young Adult
DNA
endoscopic ultrasound-guided fine needle aspiration
pancreatic carcinoma
pancreatic ductal carcinoma
pancreatic neoplasms
sequence analysis
Journal
Cancer cytopathology
ISSN: 1934-6638
Titre abrégé: Cancer Cytopathol
Pays: United States
ID NLM: 101499453
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
31
01
2020
revised:
01
05
2020
accepted:
21
05
2020
pubmed:
1
7
2020
medline:
24
2
2021
entrez:
30
6
2020
Statut:
ppublish
Résumé
Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a sensitive and specific tool in the risk stratification of pancreatic lesions, including cysts. The sensitivity and specificity of EUS-FNA has been shown to improve when cytology is combined with next-generation sequencing (NGS). Ideally, fresh cyst fluid is used for NGS. In this pilot study, we explore the possibility of sequencing DNA derived from residual alcohol-fixed pancreatic aspirates. Residual cytologic fixatives (n = 42) from 39 patients who underwent EUS-FNA for pancreatic lesions were collected along with demographics, imaging, and laboratory studies. Samples were designated as nonneoplastic/nonmucinous benign (NB), mucinous cyst (MC), pancreatic ductal adenocarcinoma (PDAC), or well-differentiated neuroendocrine tumor (NET) on the basis of cytopathologic evaluation and sequenced on the Oncomine platform (ThermoFisher Scientific, Waltham, Massachusetts). Ten of 14 (71.4%) MCs exhibited clinically significant variants, including KRAS, GNAS, and TP53. Ten of 15 (66.7%) PDACs had KRAS alterations, and 9 of 15 (60%) showed variants in TP53. No variants were detected in any NETs. Only 1 of 9 (11.1%) NB aspirates showed variants in KRAS and MAP2K. Sequencing of formalin-fixed, paraffin-embedded tissue revealed variants identical to those detected in fixative-derived DNA in 4 of 5 cases (80%). Residual DNA from alcohol-fixed aspirates are an underutilized source for NGS. Sequencing residual fixative-derived DNA has the potential to be integrated into the workup of pancreatic aspirates, possibly impacting management.
Sections du résumé
BACKGROUND
Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a sensitive and specific tool in the risk stratification of pancreatic lesions, including cysts. The sensitivity and specificity of EUS-FNA has been shown to improve when cytology is combined with next-generation sequencing (NGS). Ideally, fresh cyst fluid is used for NGS. In this pilot study, we explore the possibility of sequencing DNA derived from residual alcohol-fixed pancreatic aspirates.
METHODS
Residual cytologic fixatives (n = 42) from 39 patients who underwent EUS-FNA for pancreatic lesions were collected along with demographics, imaging, and laboratory studies. Samples were designated as nonneoplastic/nonmucinous benign (NB), mucinous cyst (MC), pancreatic ductal adenocarcinoma (PDAC), or well-differentiated neuroendocrine tumor (NET) on the basis of cytopathologic evaluation and sequenced on the Oncomine platform (ThermoFisher Scientific, Waltham, Massachusetts).
RESULTS
Ten of 14 (71.4%) MCs exhibited clinically significant variants, including KRAS, GNAS, and TP53. Ten of 15 (66.7%) PDACs had KRAS alterations, and 9 of 15 (60%) showed variants in TP53. No variants were detected in any NETs. Only 1 of 9 (11.1%) NB aspirates showed variants in KRAS and MAP2K. Sequencing of formalin-fixed, paraffin-embedded tissue revealed variants identical to those detected in fixative-derived DNA in 4 of 5 cases (80%).
CONCLUSION
Residual DNA from alcohol-fixed aspirates are an underutilized source for NGS. Sequencing residual fixative-derived DNA has the potential to be integrated into the workup of pancreatic aspirates, possibly impacting management.
Identifiants
pubmed: 32598087
doi: 10.1002/cncy.22315
pmc: PMC9285651
mid: NIHMS1794398
doi:
Substances chimiques
Biomarkers, Tumor
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
840-851Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2020 American Cancer Society.
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