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.
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.
Authors: Shuanzeng Wei; David Lieberman; Jennifer J D Morrissette; Zubair W Baloch; David B Roth; Cindy McGrath Journal: Cancer Cytopathol Date: 2015-12-18 Impact factor: 5.284
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Authors: Matthew W Rosenbaum; Martin Jones; Jonathan C Dudley; Long P Le; A John Iafrate; Martha B Pitman Journal: Cancer Cytopathol Date: 2016-09-20 Impact factor: 5.284
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Authors: Melina Arnold; Mark J Rutherford; Aude Bardot; Jacques Ferlay; Therese M-L Andersson; Tor Åge Myklebust; Hanna Tervonen; Vicky Thursfield; David Ransom; Lorraine Shack; Ryan R Woods; Donna Turner; Suzanne Leonfellner; Susan Ryan; Nathalie Saint-Jacques; Prithwish De; Carol McClure; Agnihotram V Ramanakumar; Heather Stuart-Panko; Gerda Engholm; Paul M Walsh; Christopher Jackson; Sally Vernon; Eileen Morgan; Anna Gavin; David S Morrison; Dyfed W Huws; Geoff Porter; John Butler; Heather Bryant; David C Currow; Sara Hiom; D Max Parkin; Peter Sasieni; Paul C Lambert; Bjørn Møller; Isabelle Soerjomataram; Freddie Bray Journal: Lancet Oncol Date: 2019-09-11 Impact factor: 41.316