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 - 2020/1/1
Y1 - 2020/1/1
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
KW - next-generation sequencing
KW - whole-exome sequencing
KW - EUS-FNA
KW - pancreatic ductal adenocarcinoma
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
C2 - 31552911
SN - 2303-9027
VL - 9
SP - 37
EP - 44
JO - Endoscopic Ultrasound
JF - Endoscopic Ultrasound
IS - 1
ER -