Purpose:
Pancreatic cysts are common and pose diagnostic and management challenges.
Pancreatic cyst fluid markers have the potential to aid in the management of
cysts with concerning imaging findings. Our aim was to evaluate cyst fluid methylated
DNA markers for their accuracy for predicting the histologic grade of neoplastic
pancreatic cysts.Experimental Design:
Pancreatic cyst fluid samples from 183 patients (29 discovery and 154 validation) aspirated after surgical resection were analyzed for methylated
DNA at selected genes (SOX17, BNIP3, FOXE1, PTCHD2, SLIT2, EYA4, and SFRP1) using methylation-specific droplet-digital PCR (dd-QMSP). Methylated
DNA levels were evaluated for their accuracy at predicting the grade of dysplasia of the
pancreatic cyst.Results: All six markers evaluated in the validation set could accurately distinguish high-risk
cystic neoplasms (with high-grade dysplasia and/or associated invasive
cancer) from low-risk
cysts (lower grades of dysplasia) with accuracies from 79.8% to 83.6%. Methylated SOX17 had the highest overall accuracy as a single marker (sensitivity, 78.4%; specificity, 85.6%; accuracy 83.6%, cutoff; 25 methylated
DNA molecules/μL cyst fluid). The best four-gene combination had 84.3% sensitivity, 89.4% specificity, and 88.0% accuracy at distinguishing
cysts with high-grade dysplasia and/or invasive
cancer from those without. All six markers were independent predictors of having invasive
cancer/high-grade dysplasia after adjusting for clinical/imaging factors known to be associated with grade of dysplasia. The combination of methylated SOX17 with cytology better predicted neoplastic grade than cytology alone.Conclusions: A panel of methylated gene markers quantified by dd-QMSP can be used to predict the grade of dysplasia of
pancreatic cysts. Clin
Cancer Res; 23(14); 3935-44. ©2017 AACR.