Introduction: Management of pancreatic mucinous cyst may be contingent upon its identity as intraductal papillary mucinous neoplasm (IPMN) or mucinous cystadenoma. IPMNs, although unifocal on presentation, develop multifocality and cyst size is not a predictor of malignant potential. Conversely, mucinous cystadenomas are rarely multifocal and thus amenable to segmental resection/enucleation, and cyst size is a predictor of malignant potential. Distinguising between IPMN and mucinous cystadenoma is clinically important, necessitating novel biomarkers of degrees of IPMN dysplasia. Preliminary studies suggest a positive correlation of cyclooxygenase-2 (COX-2) expression with IPMN dysplasia. We hypothesized that prostaglandin E₂ (PGE₂), a measure of cyclooxygenase activity, distinguishes between IPMN and mucinous cystadenoma and may be a biomarker of IPMN dysplasia.
Methods: Fifty patients signed informed consent for collection of pancreatic cyst and/or ductal fluid at the time of endoscopy (EUS or ERCP) or operation (OR). Pancreatic fluid was analyzed by PGE₂ ELISA. Secretin was used to enhance ductal fluid yield. Secretin decreased PGE₂ level 5X (3±0.9 without vs 0.6±0.2 with; p<0.05) when the same patient was used as a control, which was adjusted in overall analyses. COX inhibitor medication use was recorded. COX inhibitor use did not influence PGE₂ level when compared to the mean PGE₂ of the category in question. PGE₂ level was correlated with surgical pathologic diagnosis and stage.
Results: Mean PGE₂ level (pg/μl) in IPMNs (2.3±0.6) was greater than in mucinous cystadenomas (0.2±0.1) (p<0.05). In comparison, serous cystadenomas had a mean PGE₂ level of 0.2±0.1. Mean PGE₂ level of IPMN by stage was 13.3±2.3 (invasive), 4.4±0.9 (carcinoma, i.e., carcinoma-in-situ), 1.3±0.4 (borderline), and 0.1±0.01 (adenoma). Thus, only IPMN adenoma grade attained the PGE₂ range of mucinous cystadenomas. With progression of IPMN from adenoma to invasive, PGE₂ showed a significant stepwise increase. By comparison, ductal fluid in patients with ductal adenocarcinoma not associated with IPMN had a mean PGE₂ level of 4.8±1.4. In IPMN fluid samples, there was no difference in PGE₂ level in duct fluid compared to cyst fluid, OR- vs. EUS-acquired cyst fluid or OR- vs. ERCP-acquired ductal fluid.
Conclusions: PGE₂ level may be useful in predicting IPMN over mucinous cystadenoma in patients with suspected mucinous lesions based on cytology, mucin or elevated CEA. PGE₂ level may also be a useful indicator of malignant progression of IPMN if followed longitudinally, and thus COX inhibitors deserve further study as chemopreventative agents in IPMN.