Expression of MSX2 predicts malignancy of branch duct intraductal papillary mucinous neoplasm of the pancreas

Background: To distinguish malignant from benign branch duct (BD)-intraductal papillary mucinous neoplasm (IPMN) still remains difficult. Recently, we revealed that MSX2 was frequently expressed in pancreatic cancer and its expression was correlated with aggressive behavior of the cancer. The aim of this study was to assess the involvement of MSX2 in IPMN development and whether its expression would differentiate malignant from benign IPMN. Methods: Seventeen microdissected lesions and 45 IPMN tissues were used for quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) and immunohistochemistry, respectively. The role of MSX2 in the pancreatic duct cell was assessed by the induced expression of MSX2 in a normal human pancreatic duct epithelial cell line (HPDE). Results: Malignant IPMN expressed significantly higher levels of MSX2 mRNA than benign IPMN lesions. MSX2 protein expression was frequently found in borderline and malignant lesions (20/29, 68.9%), while its expression was seen in only one of 16 benign IPMN tissues. Univariate analysis showed that nodules of 6 mm or more and MSX2 expression were significantly correlated with the malignancy of BD-IPMN (P = 0.022 and 0.0026, respectively), and multivariate analysis revealed that only MSX2 expression was identified as an independent factor to predict malignant BD-IPMN. HPDE cells expressing MSX2 showed increased cellular proliferation compared to control cells. Conclusions: Based on our results, MSX2 plays a pivotal role in the development of IPMN through growth stimulation of tumor cells, and its expression was identified as an independent predictive factor for malignancy of BD-IPMN.