Published online Sep 28, 2019. doi: 10.3748/wjg.v25.i36.5530
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
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.
To confirm whether CF genomic profiles are a reliable malignancy predictor by comparing NGS mutational analyses of CF and NT.
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.
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.
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.