Next-generation sequencing of residual cytologic fixative preserved DNA from pancreatic lesions: A pilot study.
Fulmer CG; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.; Robert J. Tomsich Pathology and Laboratory Medicine Institute, The Cleveland Clinic, Cleveland, Ohio.
Park K; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Dilcher T; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Ho M; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Mirabelli S; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Alperstein S; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Hissong EM; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Pittman M; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Siddiqui M; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Heymann JJ; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Yantiss RK; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Borczuk AC; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Fernandes H; Department of Pathology and Cell Biology, Columbia University Irving Medical Center, New York, New York.
Sigel C; Department of Pathology, The Memorial Sloan Kettering Cancer Center, New York, New York.
Song W; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.
Mosquera JM; Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, New York.; Englander Institute for Precision Medicine, Weill Cornell Medicine, New York, New York.
Rao R; The Leopold G. Koss Division of Cytology, The Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York.
Cancer cytopathology [Cancer Cytopathol] 2020 Nov; Vol. 128 (11), pp. 840-851. Date of Electronic Publication: 2020 Jun 29.
Typ publikacji :
Imprint Name(s) :
Original Publication: Hoboken, NJ : Wiley-Blackwell
MeSH Terms :
Carcinoma, Pancreatic Ductal/*diagnosis
High-Throughput Nucleotide Sequencing/*methods
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/surgery ; Cytological Techniques ; Endoscopic Ultrasound-Guided Fine Needle Aspiration ; Female ; Humans ; Male ; Middle Aged ; Neuroendocrine Tumors/genetics ; Neuroendocrine Tumors/surgery ; Pancreatic Cyst/genetics ; Pancreatic Cyst/surgery ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/surgery ; Pilot Projects ; Prognosis ; Specimen Handling ; Young Adult
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Contributed Indexing :
Keywords: DNA*; endoscopic ultrasound-guided fine needle aspiration*; pancreatic carcinoma*; pancreatic ductal carcinoma*; pancreatic neoplasms*; sequence analysis*
Substance Nomenclature :
0 (Biomarkers, Tumor)
Entry Date(s) :
Date Created: 20200630 Date Completed: 20210223 Latest Revision: 20210223
Update Code :
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.
(© 2020 American Cancer Society.)