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Title

Somatic molecular analysis augments cytologic evaluation of pancreatic cyst fluids as a diagnostic tool

Authors

Ali Sakhdari, University of Massachusetts Medical SchoolFollow
Parnian Ahmadi Moghaddam, University of Massachusetts Medical SchoolFollow
Chi Young Ok, University of Massachusetts Medical School
Otto Walter, University of Massachusetts Medical School
Keith Tomaszewicz, University of Massachusetts Medical SchoolFollow
Mandi-Lee Caporelli, University of Massachusetts Medical SchoolFollow
Xiuling Meng, University of Massachusetts Medical SchoolFollow
Jennifer LaFemina, University of Massachusetts Medical SchoolFollow
Giles F. Whalen, University of Massachusetts Medical SchoolFollow
Edward Belkin, University of Massachusetts Medical SchoolFollow
Jaroslav Zivny, University of Massachusetts Medical SchoolFollow
Wahid Y. Wassef, University of Massachusetts Medical SchoolFollow
Bruce A. Woda, University of Massachusetts Medical SchoolFollow
Lloyd Hutchinson, University of Massachusetts Medical SchoolFollow
Ediz F. Cosar, University of Massachusetts Medical SchoolFollow

UMMS Affiliation

Department of Pathology; Department of Surgery; Department of Medicine

Publication Date

2019-06-18

Document Type

Article

Disciplines

Cancer Biology | Cell Biology | Diagnosis | Fluids and Secretions | Neoplasms | Oncology

Abstract

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.

Keywords

molecular next generation sequencing, non-diagnostic cytology, pancreatic cyst classification

Rights and Permissions

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.

DOI of Published Version

10.18632/oncotarget.26999

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

Journal/Book/Conference Title

Oncotarget professional or personal) to report.

Related Resources

Link to Article in PubMed

PubMed ID

31258847

Repository Citation

Sakhdari, Ali; Moghaddam, 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; and Cosar, Ediz F., "Somatic molecular analysis augments cytologic evaluation of pancreatic cyst fluids as a diagnostic tool" (2019). Open Access Articles. 3895.
https://escholarship.umassmed.edu/oapubs/3895

Creative Commons License

This work is licensed under a Creative Commons Attribution 3.0 License.