Copyright
©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
Genomic profile concordance between pancreatic cyst fluid and neoplastic tissue
Arthur Laquière, Arnaud Lagarde, Bertrand Napoléon, Raphaël Bourdariat, Alexandre Atkinson, Gianfranco Donatelli, Bernard Pol, Laurence Lecomte, Laurence Curel, Romina Urena-Campos, Thierry Helbert, Vincent Valantin, François Mithieux, Jean Pascal Buono, Philippe Grandval, Sylviane Olschwang
Arthur Laquière, Laurence Lecomte, Romina Urena-Campos, Department of Gastroenterology, Saint Joseph Hospital, Marseille 13008, France
Arnaud Lagarde, Alexandre Atkinson, Philippe Grandval, Sylviane Olschwang, Aix-Marseille Univ, INSERM, MMG, Marseille 13385, France
Arnaud Lagarde, AP-HM, Conception Hospital, Marseille 13385, France
Bertrand Napoléon, Raphaël Bourdariat, François Mithieux, RGDS, Jean Mermoz Hospital, Lyon 69008, France
Gianfranco Donatelli, RGDS, Les Peupliers Hospital, Paris 75013, France
Bernard Pol, Department of Digestive Surgery, Saint-Joseph Hospital, Marseille 13008, France
Laurence Curel, Department of Clinical Research, Saint Joseph Hospital, Marseille 13008, France
Thierry Helbert, Vincent Valantin, Sylviane Olschwang, European Hospital, Marseille 13003, France
Jean Pascal Buono, Pathological Anatomy and Cytology, MEDIPATH, Eguilles 13510, France
Philippe Grandval, Sylviane Olschwang, AP-HM, Timone Hospital, Marseille 13005, France
Sylviane Olschwang, RGDS, Clairval Hospital, Marseille 13009, France
Author contributions: Laquière AE and Lagarde A provided equal contributions to the study and the article; All authors met the three conditions of authorship published by the ICMJE: Substantial contribution to conception and design, data acquisition analysis, and interpretation/drafting the article, and making critical revisions/final approval of the final version.
Institutional review board statement: This study has been reviewed by the institutional review board of the Saint Joseph Hospital.
Clinical trial registration statement: This study is registered at https://clinicaltrials.gov/ct2/show/NCT03305146?term=cyst+gen&rank=1. The registration identification number is [NCT03305146].
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrolment. All involved persons (subjects or legally authorized representative) gave their written informed consent prior to study inclusion.
Conflict-of-interest statement: The authors do not have any conflicts of interest to disclose.
CONSORT 2010 statement: The authors have read the CONSORT 2010 Statement, and the manuscript was prepared and revised according to the CONSORT 2010 Statement.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Arthur Laquière, MD, Hepatogastroenterologist, Department of Gastroenterology, Saint Joseph Hospital, 26 bd de Louvain, Marseille 13008, France.
alaquiere@gmail.com
Telephone: +33-4-91801822 Fax: +33-4-91806912
Received: April 30, 2019
Peer-review started: April 30, 2019
First decision: May 30, 2019
Revised: July 16, 2019
Accepted: August 19, 2019
Article in press: Auguet 19, 2019
Published online: September 28, 2019
Processing time: 151 Days and 18.1 Hours
BACKGROUND
DNA mutational analysis of pancreatic cystic fluid (CF) is a useful adjunct to the evaluation of pancreatic cysts. KRAS/GNAS or RAF/PTPRD/CTNNB1/RNF43 mutations are highly specific to precancerous or advanced neoplasia. Several studies recently demonstrated the ability of next-generation sequencing (NGS) analysis to detect DNA mutations in pancreatic CF, but few studies have performed a systematic comparative analysis between pancreatic CF and neoplastic surgical tissue (NT). The value of CF-NGS analysis indicators for determining surgical resection necessitates evaluation.
AIM
To confirm whether CF genomic profiles are a reliable malignancy predictor by comparing NGS mutational analyses of CF and NT.
METHODS
Patients requiring surgery for high-risk pancreatic cysts were included in a multicenter prospective pilot study. DNA from CF (collected by endoscopic ultrasound-guided fine needle aspiration (known as EUS-FNA)) and NT (collected by surgery) were analyzed by NGS. The primary objective was to compare the mutation profiles of paired DNA samples. The secondary objective was to correlate the presence of specific mutations (KRAS/GNAS, RAF/ PTPRD/CTNNB1/RNF43/POLD1/TP53) with a final cancer diagnosis. Sensitivity and specificity were also evaluated.
RESULTS
Between December 2016 and October 2017, 20 patients were included in this pilot study. Surgery was delayed for 3 patients. Concordant CF-NT genotypes were found in 15/17 paired DNA, with a higher proportion of mutated alleles in CF than in NT. NGS was possible for all pancreatic CF collected by EUS-FNA. In 2 cases, the presence of a KRAS/GNAS mutation was discordant between CF and NT. No mutations were found in 3 patients with NT or pancreatic cysts with high-grade dysplasia. The sensitivity and specificity of KRAS/GNAS mutations in CF to predict an appropriate indication for surgical resection were 0.78 and 0.62, respectively. The sensitivity and specificity of RAF/PTPRD/CTNNB1 /RNF43/POLD1/TP53 mutations in CF were 0.55 and 1.0, respectively.
CONCLUSION
Mutational analyses of CF and NT were highly concordant, confirming the value of NGS analysis of CF in the preoperative malignancy assessment. However, these results need to be confirmed on a larger scale.
Core tip: This pilot study (20 patients) was a comparative next-generation sequencing mutational analysis between pancreatic cyst fluid (CF) and neoplastic surgical tissue (NT) to confirm whether the CF genomic profile was a reliable malignancy predictor. Concordant genotypes were found in 15 of 17 paired DNA samples. The sensitivity and specificity of CF mutations to predict an appropriate indication for surgical resection were 0.78 and 0.62 for the KRAS/GNAS mutations and 0.55 and 1.0 for the RAF/PTPRD/CTNNB1/RNF43/POLD1/TP53 mutations, respectively. Mutational analyses of CF and NT were highly concordant, confirming the interest of CF next-generation sequencing analysis in the preoperative malignancy assessment.
