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DNA sequencing of cytopathologically inconclusive EUS-FNA from solid pancreatic lesions suspicious for malignancy confirms EUS diagnosis

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@article{914d0ea37c1a4c14abe68c88e7da48c3,
title = "DNA sequencing of cytopathologically inconclusive EUS-FNA from solid pancreatic lesions suspicious for malignancy confirms EUS diagnosis",
abstract = "Background and Objectives: EUS-FNA is inconclusive in up to 10{\%}-15{\%} of patients with solid pancreatic lesions (SPLs). We aimed to investigate whether supplementary genetic analyses with whole-exome sequencing add diagnostic value in patients with SPLs suspicious of malignancy but inconclusive EUS-FNA.Patients and Methods: Thirty-nine patients, who underwent EUS-FNA of an SPL were retrospectively included. Three groups were defined: 16 (41.0{\%}) had suspected malignancy on EUS confirmed by cytology (malignant), 13 (33.3{\%}) had suspected malignancy on EUS but benign cytology (inconclusive), and 10 (25.6{\%}) had benign EUS imaging and cytology (benign). Areas with the highest epithelial cell concentrations were macro-dissected from the FNA smears from each patient, and extracted DNA was used for whole-exome sequencing by next-generation sequencing of a selected gene panel including 19 genes commonly mutated in cancer.Results: Pathogenic mutations in K-RAS, TP53, and PIK3CA differed significantly between the three groups (P < 0.001, P = 0.018, and P = 0.026, respectively). Pathogenic mutations in KRAS and TP53 were predominant in the inconclusive (54{\%} and 31{\%}, respectively) and malignant groups (81.3{\%} and 50{\%}, respectively) compared to the benign group (0{\%}). Malignant and inconclusive diagnoses correlated strongly with poor overall survival (P < 0.001).Conclusion: Whole-exome sequencing of genes commonly mutated in pancreatic cancer may be an important adjunct in patients with SPLs suspicious for malignancy on EUS but with uncertain cytological diagnosis.",
keywords = "Diagnostics, EUS-FNA, next-generation sequencing, Pancreatic ductal adenocarcinoma, Whole-exome sequencing",
author = "Plougmann, {Julie Isabelle} and Pia Klausen and Anders Toxvaerd and Abedi, {Armita Armina} and Bojan Kovacevic and Karstensen, {John G{\'a}sdal} and Poulsen, {Tim Svenstrup} and Evangelos Kalaitzakis and Estrid H{\o}gdall and Peter Vilmann",
year = "2020",
month = "1",
doi = "10.4103/eus.eus_36_19",
language = "English",
volume = "9",
pages = "37--44",
journal = "Endoscopic Ultrasound",
issn = "2303-9027",
publisher = "Medknow Publications and Media Pvt. Ltd",
number = "1",

}

RIS

TY - JOUR

T1 - DNA sequencing of cytopathologically inconclusive EUS-FNA from solid pancreatic lesions suspicious for malignancy confirms EUS diagnosis

AU - Plougmann, Julie Isabelle

AU - Klausen, Pia

AU - Toxvaerd, Anders

AU - Abedi, Armita Armina

AU - Kovacevic, Bojan

AU - Karstensen, John Gásdal

AU - Poulsen, Tim Svenstrup

AU - Kalaitzakis, Evangelos

AU - Høgdall, Estrid

AU - Vilmann, Peter

PY - 2020/1

Y1 - 2020/1

N2 - Background and Objectives: EUS-FNA is inconclusive in up to 10%-15% of patients with solid pancreatic lesions (SPLs). We aimed to investigate whether supplementary genetic analyses with whole-exome sequencing add diagnostic value in patients with SPLs suspicious of malignancy but inconclusive EUS-FNA.Patients and Methods: Thirty-nine patients, who underwent EUS-FNA of an SPL were retrospectively included. Three groups were defined: 16 (41.0%) had suspected malignancy on EUS confirmed by cytology (malignant), 13 (33.3%) had suspected malignancy on EUS but benign cytology (inconclusive), and 10 (25.6%) had benign EUS imaging and cytology (benign). Areas with the highest epithelial cell concentrations were macro-dissected from the FNA smears from each patient, and extracted DNA was used for whole-exome sequencing by next-generation sequencing of a selected gene panel including 19 genes commonly mutated in cancer.Results: Pathogenic mutations in K-RAS, TP53, and PIK3CA differed significantly between the three groups (P < 0.001, P = 0.018, and P = 0.026, respectively). Pathogenic mutations in KRAS and TP53 were predominant in the inconclusive (54% and 31%, respectively) and malignant groups (81.3% and 50%, respectively) compared to the benign group (0%). Malignant and inconclusive diagnoses correlated strongly with poor overall survival (P < 0.001).Conclusion: Whole-exome sequencing of genes commonly mutated in pancreatic cancer may be an important adjunct in patients with SPLs suspicious for malignancy on EUS but with uncertain cytological diagnosis.

AB - Background and Objectives: EUS-FNA is inconclusive in up to 10%-15% of patients with solid pancreatic lesions (SPLs). We aimed to investigate whether supplementary genetic analyses with whole-exome sequencing add diagnostic value in patients with SPLs suspicious of malignancy but inconclusive EUS-FNA.Patients and Methods: Thirty-nine patients, who underwent EUS-FNA of an SPL were retrospectively included. Three groups were defined: 16 (41.0%) had suspected malignancy on EUS confirmed by cytology (malignant), 13 (33.3%) had suspected malignancy on EUS but benign cytology (inconclusive), and 10 (25.6%) had benign EUS imaging and cytology (benign). Areas with the highest epithelial cell concentrations were macro-dissected from the FNA smears from each patient, and extracted DNA was used for whole-exome sequencing by next-generation sequencing of a selected gene panel including 19 genes commonly mutated in cancer.Results: Pathogenic mutations in K-RAS, TP53, and PIK3CA differed significantly between the three groups (P < 0.001, P = 0.018, and P = 0.026, respectively). Pathogenic mutations in KRAS and TP53 were predominant in the inconclusive (54% and 31%, respectively) and malignant groups (81.3% and 50%, respectively) compared to the benign group (0%). Malignant and inconclusive diagnoses correlated strongly with poor overall survival (P < 0.001).Conclusion: Whole-exome sequencing of genes commonly mutated in pancreatic cancer may be an important adjunct in patients with SPLs suspicious for malignancy on EUS but with uncertain cytological diagnosis.

KW - Diagnostics

KW - EUS-FNA, next-generation sequencing

KW - Pancreatic ductal adenocarcinoma

KW - Whole-exome sequencing

UR - http://www.scopus.com/inward/record.url?scp=85079854037&partnerID=8YFLogxK

U2 - 10.4103/eus.eus_36_19

DO - 10.4103/eus.eus_36_19

M3 - Journal article

VL - 9

SP - 37

EP - 44

JO - Endoscopic Ultrasound

JF - Endoscopic Ultrasound

SN - 2303-9027

IS - 1

ER -

ID: 58033330