Next-generation sequencing of residual cytologic fixative preserved DNA from pancreatic lesions: A pilot study. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • June 29, 2020

Research

keywords

  • Biomarkers, Tumor
  • Carcinoma, Pancreatic Ductal
  • High-Throughput Nucleotide Sequencing
  • Mutation
  • Neuroendocrine Tumors
  • Pancreatic Cyst
  • Pancreatic Neoplasms

Identity

Scopus Document Identifier

  • 85087144137

Digital Object Identifier (DOI)

  • 10.1002/cncy.22315

PubMed ID

  • 32598087

Additional Document Info

volume

  • 128

issue

  • 11