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


1 Division of Endoscopy, Gastro Unit, Copenhagen University Hospital, Herlev, Denmark
2 Department of Pathology, Copenhagen University Hospital Herlev, Herlev, Denmark
3 Division of Surgery, Gastro Unit, Copenhagen University Hospital, Hvidovre, Denmark

Correspondence Address:
Julie Isabelle Plougmann,
Division of Endoscopy, Gastro Unit, Copenhagen University Hospital Herlev, Herlev Ringvej 75, 2730 Herlev
Denmark
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/eus.eus_36_19

PMID: 31552911

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.


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    -  Plougmann JI
    -  Klausen P
    -  Toxvaerd A
    -  Abedi AA
    -  Kovacevic B
    -  Karstensen JG
    -  Poulsen TS
    -  Kalaitzakis E
    -  Høgdall E
    -  Vilmann P
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