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Genomic profile concordance between pancreatic cyst fluid and neoplastic tissue

World Journal of Gastroenterology 2019年第36期25卷 5530-5542页

作者： Arthur Laquière Arnaud Lagarde Bertrand Napoléon Raphael Bourdariat Alexandre Atkinson Gianfranco Donatelli Bernard Pol laurence lecomte laurence Curel Romina Urena-Campos Thierry Helbert Vincent Valantin Francois Mithieux Jean Pascal Buono Philippe Grandval Sylviane Olschwang Department of Gastroenterology Saint Joseph Hospital Marseille 13008 France AP-HM Timone Hospital Marseille 13005 France RGDS Clairval Hospital Marseille 13009 France Aix-Marseille Univ INSERM MMG Marseille 13385 France AP-HM Conception Hospital Marseille 13385 France RGDS Jean Mermoz Hospital Lyon 69008 France RGDS Les Peupliers Hospital Paris 75013 France Department of Digestive Surgery Saint-Joseph Hospital Marseille 13008 France Department of Clinical Research Saint Joseph Hospital Marseille 13008 France European Hospital Marseille 13003 France Pathological Anatomy and Cytology MEDIPATH Eguilles 13510 France

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 mutatio

关键词： Pancreatic cancer Pancreatic cystic neoplasms Pancreatic adenocarcinoma Malignancy prediction Neoplastic surgical tissue Pancreatic cystic fluid Molecular analysis Next-generation sequencing DNA mutations

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