Joseph R Habib1, Yayun Zhu1, Lingdi Yin1, Ammar A Javed1, Ding Ding1, Jonathan Tenior1, Michael Wright1, Syed Z Ali2, Richard A Burkhart1,3, William Burns1,3, Christopher L Wolfgang1,2,3, Eunji Shin4, Jun Yu5, Jin He6,7. 1. Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Baltimore, MD, 21287, USA. 2. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. 3. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. 4. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. 5. Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Baltimore, MD, 21287, USA. jyu41@jhmi.edu. 6. Department of Surgery, Johns Hopkins University School of Medicine, 600 N. Wolfe St, Baltimore, MD, 21287, USA. jhe11@jhmi.edu. 7. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, 21287, USA. jhe11@jhmi.edu.
Abstract
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.
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.
Authors: Yuri E Nikiforov; Sally E Carty; Simon I Chiosea; Christopher Coyne; Umamaheswar Duvvuri; Robert L Ferris; William E Gooding; Shane O LeBeau; N Paul Ohori; Raja R Seethala; Mitchell E Tublin; Linwah Yip; Marina N Nikiforova Journal: Thyroid Date: 2015-09-10 Impact factor: 6.568