Intracellular localization of mesothelin predicts patient prognosis of extrahepatic bile duct cancer
Intracellular localization of mesothelin predicts patient prognosis of extrahepatic bile duct cancer
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DOI：
10.3892/ijo.2012.1662
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发表时间：
2012-12-01
影响因子：
5.2
通讯作者：
Todo, Satoru
中科院分区：
文献类型：
--
作者：
Kawamata, Futoshi;Kamachi, Hirofumi;Todo, Satoru
间皮素在各种类型的恶性肿瘤中表达，我们最近报道了间皮素的表达与胰腺导管腺癌和胃腺癌患者的不良预后有关。在这项研究中，我们研究了肝外胆管癌（EHBDCA）中间皮素表达的临床病理意义，特别是其与染色模式的关系。对61例EHBDCA（肝门部胆管癌16例，胆管上段腺癌17例，胆管中段腺癌20例，胆管远端腺癌8例）的组织标本进行了化学发光检测。肿瘤细胞中间皮素的表达水平除了根据常规分析的染色强度和比例分为高和低外，还分为间皮素在腔膜和/或细胞质中的定位。间皮素的“高水平表达”（47.5%）与肝转移（P=0.013）和较差的患者预后（P=0.022）具有统计学相关性，而间皮素的“管腔”膜阳性“（52.5%）与肝转移（P=0.006）、腹膜转移（P=0.024）和不利的患者预后（P=0.017）更显著相关。此外，我们发现从间皮素的“管腔膜阴性”中分离的“细胞质表达”在整个研究中代表了最好的患者预后。我们描述了间皮素的表达模式水平，间皮素在细胞膜或细胞质中的高、低水平表达，提示间皮素可能通过其在细胞内的定位而发挥促癌作用。
Mesothelin is expressed in various types of malignant tumors, and we recently reported that the expression of mesothelin was related to unfavorable patient outcome in pancreatic ductal adenocarcinoma and gastric adenocarcinoma. In this study, we examined the clinicopathological significance of mesothelin expression in extrahepatic bile duct cancer (EHBDCA), especially in terms of its association with the staining pattern. Tissue samples from 61 EHBDCA (16 hilar cholangiocarcinoma, 17 upper bile duct adenocarcinoma, 20 middle bile duct adenocarcinoma and 8 distal bile duct adenocarcinoma) were immunohistochemically examined. The expression levels of mesothelin in tumor cells was classified into the localization of mesothelin in luminal membrane and/or cytoplasm, in addition to high and low according to the staining intensity and proportion as a conventional analysis. 'High-level expression' of mesothelin (47.5%) was statistically correlated with liver metastasis (P=0.013) and poorer patient outcome (P=0.022), while 'luminal' membrane positive' of mesothelin (52.5%) was more significantly correlated with liver metastasis (P=0.006), peritoneal metastasis (P=0.024) and unfavorable patient outcome (P=0.017). Moreover, we found that 'cytoplasmic expression' isolated from 'luminal membrane negative' of mesothelin represented the best patient prognosis throughout this study. We describe the expression pattern level of mesothelin, i.e., in luminal membrane or cytoplasm both high and low level, evidently indicate the patient prognosis of EH BDCA, suggesting the pivotal role of mesothelin in cancer promotion depending on its intracellular localization.