Division of Gastroenterology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aobaku, Sendai, Miyagi, 980-8574, Japan.
J Gastroenterol. 2010 Jul;45(7):763-70. doi: 10.1007/s00535-010-0200-1. Epub 2010 Jan 28.
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.
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).
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.
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.
区分良恶性分支胆管（BD）-导管内乳头状黏液性肿瘤（IPMN）仍然具有挑战性。最近，我们发现 MSX2 在胰腺癌中频繁表达，其表达与癌症的侵袭性行为相关。本研究旨在评估 MSX2 在 IPMN 发展中的作用，以及其表达是否能区分良恶性 IPMN。
使用 17 个微切割病变和 45 个 IPMN 组织进行定量实时逆转录聚合酶链反应（RT-PCR）和免疫组织化学分析。通过在正常人类胰腺导管上皮细胞系（HPDE）中诱导 MSX2 的表达，评估 MSX2 在胰腺导管细胞中的作用。
恶性 IPMN 的 MSX2 mRNA 表达水平明显高于良性 IPMN 病变。MSX2 蛋白表达在交界性和恶性病变中频繁出现（20/29，68.9%），而在 16 个良性 IPMN 组织中仅见 1 例。单因素分析显示，6mm 或更大的结节和 MSX2 表达与 BD-IPMN 的恶性程度显著相关（P=0.022 和 0.0026），多因素分析显示，只有 MSX2 表达被确定为预测 BD-IPMN 恶性的独立因素。表达 MSX2 的 HPDE 细胞与对照细胞相比，细胞增殖增加。
基于我们的结果，MSX2 通过肿瘤细胞的生长刺激在 IPMN 的发展中发挥关键作用，其表达被确定为 BD-IPMN 恶性的独立预测因子。
