Somatic molecular analysis augments cytologic evaluation of pancreatic cyst fluids as a diagnostic tool
Authors
Sakhdari, AliMoghaddam, Parnian Ahmadi
Ok, Chi Young
Walter, Otto
Tomaszewicz, Keith
Caporelli, Mandi-Lee
Meng, Xiuling
LaFemina, Jennifer
Whalen, Giles F.
Belkin, Edward
Zivny, Jaroslav
Wassef, Wahid Y.
Woda, Bruce A.
Hutchinson, Lloyd
Cosar, Ediz F.
Document Type
Journal ArticlePublication Date
2019-06-18Keywords
molecular next generation sequencingnon-diagnostic cytology
pancreatic cyst classification
Cancer Biology
Cell Biology
Diagnosis
Fluids and Secretions
Neoplasms
Oncology
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Show full item recordAbstract
Objective: Better tools are needed for early diagnosis and classification of pancreatic cystic lesions (PCL) to trigger intervention before neoplastic precursor lesions progress to adenocarcinoma. We evaluated the capacity of molecular analysis to improve the accuracy of cytologic diagnosis for PCL with an emphasis on non-diagnostic/negative specimens. Design: In a span of 7 years, at a tertiary care hospital, 318 PCL endoscopic ultrasound-guided fine needle aspirations (EUS-FNA) were evaluated by cytologic examination and molecular analysis. Mucinous PCL were identified based on a clinical algorithm and 46 surgical resections were used to verify this approach. The mutation allele frequency (MAF) of commonly altered genes (BRAF, CDKN2A, CTNNB1, GNAS, RAS, PIK3CA, PTEN, SMAD4, TP53 and VHL) was evaluated for their ability to identify and grade mucinous PCL. Results: Cytology showed a diagnostic sensitivity of 43.5% for mucinous PCL due in part to the impact of non-diagnostic (28.8%) and negative (50.5%) specimens. Incorporating an algorithmic approach or molecular analysis markedly increased the accuracy of cytologic evaluation. Detection of mucinous PCL by molecular analysis was 93.3% based on the detection of KRAS and/or GNAS gene mutations (p = 0.0001). Additional genes provided a marginal improvement in sensitivity but were associated with cyst type (e.g. VHL) and grade (e.g. SMAD4). In the surgical cohort, molecular analysis and the proposed algorithm showed comparable sensitivity (88.9% vs. 100%). Conclusions: Incorporating somatic molecular analysis in the cytologic evaluation of EUS-FNA increases diagnostic accuracy for detection, classification and grading of PCL. This approach has the potential to improve patient management.Source
Oncotarget. 2019 Jun 18;10(40):4026-4037. doi: 10.18632/oncotarget.26999. eCollection 2019 Jun 18. Link to article on publisher's site
DOI
10.18632/oncotarget.26999Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41106PubMed ID
31258847Related Resources
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Copyright : © 2019 Sakhdari et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Distribution License
http://creativecommons.org/licenses/by/3.0/ae974a485f413a2113503eed53cd6c53
10.18632/oncotarget.26999
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Except where otherwise noted, this item's license is described as Copyright : © 2019 Sakhdari et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.