Expression of MSX2 predicts malignancy of branch duct intraductal papillary mucinous neoplasm of the pancreas
Expression of MSX2 predicts malignancy of branch duct intraductal papillary mucinous neoplasm of the pancreas
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DOI：
10.1007/s00535-010-0200-1
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发表时间：
2010-07-01
影响因子：
6.3
通讯作者：
Shimosegawa, Tooru
中科院分区：
文献类型：
--
作者：
Satoh, Kennichi;Hamada, Shin;Shimosegawa, Tooru
分支导管内乳头状黏液性肿瘤（IPMN）的良恶性鉴别仍是一个难题。最近，我们发现MSX 2在胰腺癌中频繁表达，并且其表达与癌症的侵袭行为相关。本研究的目的是评估MSX 2参与IPMN的发展，以及其表达是否会区分恶性和良性IPMN。17个显微解剖病变和45 IPMN组织分别用于定量实时逆转录聚合酶链反应（RT-PCR）和免疫组化。MSX 2在胰腺导管细胞中的作用通过在正常人胰腺导管上皮细胞系（HPDE）中诱导MSX 2的表达来评估。恶性IPMN表达的MSX 2 mRNA水平显著高于良性IPMN病变。MSX 2蛋白在交界性和恶性病变中的表达率为68.9%（20/29），而在16例良性IPMN中仅1例表达。单因素分析显示，6 mm或以上的结节和MSX 2表达与BD-IPMN的恶性程度显著相关（P = 0.022和0.0026，分别），多因素分析显示，只有MSX 2表达被确定为预测BD-IPMN恶性的独立因素。结果表明，MSX 2在BD-IPMN的发生发展中起着重要作用，其表达可作为BD-IPMN恶性程度的独立预测因子。
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.