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Reliable Detection of Somatic Mutations for Pancreatic Cancer in Endoscopic Ultrasonography-Guided Fine Needle Aspirates with Next-Generation Sequencing: Implications from a Prospective Cohort Study.
Habib, Joseph R; Zhu, Yayun; Yin, Lingdi; Javed, Ammar A; Ding, Ding; Tenior, Jonathan; Wright, Michael; Ali, Syed Z; Burkhart, Richard A; Burns, William; Wolfgang, Christopher L; Shin, Eunji; Yu, Jun; He, Jin.
Afiliação
  • Habib JR; Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Baltimore, MD, 21287, USA.
  • Zhu Y; Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Baltimore, MD, 21287, USA.
  • Yin L; Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Baltimore, MD, 21287, USA.
  • Javed AA; Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Baltimore, MD, 21287, USA.
  • Ding D; Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Baltimore, MD, 21287, USA.
  • Tenior J; Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Baltimore, MD, 21287, USA.
  • Wright M; Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Baltimore, MD, 21287, USA.
  • Ali SZ; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
  • Burkhart RA; Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Baltimore, MD, 21287, USA.
  • Burns W; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
  • Wolfgang CL; Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Baltimore, MD, 21287, USA.
  • Shin E; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
  • Yu J; Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Baltimore, MD, 21287, USA.
  • He J; Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA.
J Gastrointest Surg ; 25(12): 3149-3159, 2021 12.
Article em En | MEDLINE | ID: mdl-34244950
BACKGROUND OR PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is commonly diagnosed by endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). However, the diagnostic adequacy of EUS-FNA is often limited by low cellularity leading to inconclusive results. We aimed to investigate the feasibility and added utility of targeted next-generation sequencing (NGS) on PDAC EUS-FNAs. METHODS: EUS-FNAs were prospectively performed on 59 patients with suspected PDAC (2014-2017) at a high-volume center. FNAs were analyzed for the presence of somatic mutations using NGS to supplement cytopathologic evaluations and were compared to surgical specimens and circulating tumor DNA (ctDNA). RESULTS: Fifty-nine patients with suspected PDAC were evaluated, and 52 were diagnosed with PDAC on EUS-FNA. Four of the remaining seven patients had inconclusive EUS-FNAs and were ultimately diagnosed with PDAC after surgical resection. Of these 56 cases of PDAC, 48 (85.7%) and 18 (32.1%) harbored a KRAS and/or TP53 mutation on FNA NGS, respectively. Particularly, in the four inconclusive FNA PDAC diagnoses (false negatives), half harbored KRAS mutations on FNA. No KRAS/TP53 mutation was found in remaining three non-PDAC cases. All EUS-FNA detected KRAS mutations were detected in 16 patients that underwent primary tumor NGS (100% concordance), while 75% KRAS concordance was found between FNA and ctDNA NGS. CONCLUSION: Targeted NGS can reliably detect KRAS mutations from EUS-FNA samples and exhibits high KRAS mutational concordance with primary tumor and ctDNA. This suggests targeted NGS of EUS-FNA samples may enable preoperative ctDNA prognostication using digital droplet PCR and supplement diagnoses in patients with inconclusive EUS-FNA.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Endossonografia Tipo de estudo: Diagnostic_studies / Etiology_studies / Observational_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Neoplasias Pancreáticas / Endossonografia Tipo de estudo: Diagnostic_studies / Etiology_studies / Observational_studies Limite: Humans Idioma: En Ano de publicação: 2021 Tipo de documento: Article