Pancreatic cyst fluid concentration of high-mobility group A2 protein acts as a differential biomarker of dysplasia in intraductal papillary mucinous neoplasm

Background and Aims No reliable cyst fluid biomarkers exist that allow preoperative identification of patients with intraductal papillary mucinous neoplasms (IPMNs) and high-risk pathology. High-mobility group (HMG) A2 protein has been demonstrated to be a biomarker of dysplasia in IPMNs. It is unknown whether HMGA2 protein is present in the cyst fluid from IPMNs. The aims of this study were to determine whether HMGA2 protein is present in the cyst fluid of IPMNs and demonstrate whether HMGA2 protein concentration correlates with the degree of dysplasia. Methods Patients with surgically resected IPMNs and banked pancreatic cyst fluid were identified. Low-risk IPMNs (low-grade [LGD] or moderate dysplasia [MD]) and high-risk IPMNs (high-grade dysplasia [HGD] or invasive cancer) were identified. Pancreatic cyst fluid concentrations of HMGA2 protein were measured via enzyme-linked immunosorbent assay. Results Samples from 31 patients were analyzed. HMGA2 protein was detected in the cyst fluid of 30 of 31 specimens (97%). Median cyst fluid HMGA2 protein concentration (ng/mL) was as follows: LGD, 0.6 (interquartile range [IQR] 0.35-0.6); MD, 1.55 (IQR 0.65-2.7); HGD, 4.2 (IQR 1.7-9.2) (P <.05). The median HMGA2 protein concentration was significantly higher in the HGD group (4.2 ng/mL, IQR 1.7-9.2) compared with the concentration in the low-risk group (1.1 ng/mL, IQR 0.6-2.7, P =.03). Conclusion HMGA2 protein is present in IPMN cyst fluid. Significantly higher concentrations of cyst fluid HMGA2 protein are found in IPMNs with HGD compared with lesions with LGD or MD. Cyst fluid concentrations of HMGA2 protein may thus serve as a biomarker to differentiate patients with high-risk IPMNs from those with low-risk IPMNs.