Pancreatic Juice Mutation Concentrations Can Help Predict the Grade of Dysplasia in Patients Undergoing Pancreatic Surveillance

Abstract

The measurement of mutations in pancreatic juice samples collected from the duodenum during endoscopic ultrasound (EUS) may improve the diagnostic evaluation of patients undergoing pancreatic surveillance. Our aim was to evaluate the accuracy of using pancreatic juice mutation concentrations to predict the presence and histologic grade of neoplasia in the pancreas. Digital next-generation sequencing (NGS) of pancreatic juice DNA using a targeted 12-gene panel was performed on 67 patients undergoing pancreatic evaluation during EUS, including patients with pancreatic ductal adenocarcinoma, patients who subsequently underwent pancreatic resection for precursor lesions, patients undergoing surveillance for their familial/inherited susceptibility to pancreatic cancer, and normal pancreas disease controls. Patients with pancreatic cancer or high-grade dysplasia as their highest grade lesion had significantly higher pancreatic juice mutation concentrations than all other subjects (mean/SD digital NGS score; 46.6 ± 69.7 vs. 6.2 ± 11.6, = 0.02). Pancreatic juice mutation concentrations distinguished patients with pancreatic cancer or high-grade dysplasia in their resection specimen from all other subjects with 72.2% sensitivity and 89.4% specificity [area under the curve (AUC) = 0.872]. Mutant/ concentrations could distinguish patients with pancreatic cancer or high-grade dysplasia in their resection specimen from all other subjects with 61.1% sensitivity and 95.7% specificity (AUC = 0.819). Among 31 high-risk individuals under surveillance, 2 of the 3 individuals with most abnormal pancreatic juice mutation profiles also had the most abnormalities on pancreatic imaging. Pancreatic juice mutation analysis using digital NGS has potential diagnostic utility in the evaluation of patients undergoing pancreatic surveillance. .

Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium

“…Since PanIN generally do not cause specific imaging abnormalities, high-grade PanIN (previously known as PanIN-3) is diagnosed only by surgical pathology review of pancreatic resections undertaken for other concerning imaging findings. In some cases, evidence of pancreatic neoplasia can be inferred by the presence of mutations detected in secretin-stimulated pancreatic fluid samples,104 106 and multifocal PanIN lesions by imaging findings of lobulocentric atrophy,59 but further investigation is needed to determine the value of these tests for patients under pancreatic surveillance.…”

Management of Intraductal Papillary Mucinous Neoplasms: Controversies in Guidelines and Future Perspectives

“…However, more research is needed to distinguish whether the clinical value outweighs the high costs of these sensitive laboratory techniques [ 59 , 78 ]. For pancreatic juice, Suenaga et al (2018) [ 60 ] found GNAS gene mutations in 70% of patients with IPMN. Also, TP53 and SMAD-4 levels were found to be related to dysplasia grade, and able to distinguish IPMN from PDAC with a sensitivity and specificity of 32 and 100%, respectively [ 60 , 79 ].…”

“…For pancreatic juice, Suenaga et al (2018) [ 60 ] found GNAS gene mutations in 70% of patients with IPMN. Also, TP53 and SMAD-4 levels were found to be related to dysplasia grade, and able to distinguish IPMN from PDAC with a sensitivity and specificity of 32 and 100%, respectively [ 60 , 79 ]. A VHL gene mutation increases the probability of detecting a serous cyst neoplasia (SCN) [ 60 , 79 ].…”

Next‐generation sequencing of residual cytologic fixative preserved DNA from pancreatic lesions: A pilot study

“…Other than in this case, alterations in TP53 were limited to the cohort of PDACs. Suenaga et al 28 reported that the detection of TP53 and SMAD4 variants by NGS in pancreatic juice had a sensitivity of 61.1% and a specificity of 95.7% for the detection of PDAC or high‐grade dysplasia in their surveillance cohort of patients with a strong family history of pancreatic cancer, supporting the notion that some lesions are genetically high‐risk, thus necessitating more aggressive management.…”