TY - JOUR
T1 - Next-generation sequencing of residual cytologic fixative preserved DNA from pancreatic lesions
T2 - A pilot study
AU - Fulmer, Clifton G.
AU - Park, Kyung
AU - Dilcher, Thomas
AU - Ho, Mai
AU - Mirabelli, Susanna
AU - Alperstein, Susan
AU - Hissong, Erika M.
AU - Pittman, Meredith
AU - Siddiqui, Momin
AU - Heymann, Jonas J.
AU - Yantiss, Rhonda K.
AU - Borczuk, Alain C.
AU - Fernandes, Helen
AU - Sigel, Carlie
AU - Song, Wei
AU - Mosquera, Juan Miguel
AU - Rao, Rema
N1 - Publisher Copyright:
© 2020 American Cancer Society
PY - 2020/11/1
Y1 - 2020/11/1
N2 - 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.
AB - 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.
KW - DNA
KW - endoscopic ultrasound-guided fine needle aspiration
KW - pancreatic carcinoma
KW - pancreatic ductal carcinoma
KW - pancreatic neoplasms
KW - sequence analysis
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U2 - 10.1002/cncy.22315
DO - 10.1002/cncy.22315
M3 - Article
C2 - 32598087
AN - SCOPUS:85087144137
SN - 1934-662X
VL - 128
SP - 840
EP - 851
JO - Cancer Cytopathology
JF - Cancer Cytopathology
IS - 11
ER -
