Correlation of pathological grade and tumor stage of urothelial carcinomas with CD109 expression
Correlation of pathological grade and tumor stage of urothelial carcinomas with CD109 expression
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DOI：
10.1111/j.1440-1827.2010.02592.x
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发表时间：
2010-11-01
影响因子：
2.2
通讯作者：
Takahashi, Masahide
中科院分区：
文献类型：
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作者：
Hagikura, Minako;Murakumo, Yoshiki;Takahashi, Masahide
膀胱癌是最常见的恶性肿瘤之一。由于高复发率是早期尿路上皮癌的一个严重问题，因此已经探索了治疗复发性尿路上皮癌的新策略。CD 109是一种糖基磷脂酰肌醇锚定的糖蛋白，在各种癌组织中表达，主要是鳞状细胞癌。CD 109在体外负性控制转化生长因子（TGF）-β/Smad信号传导。本研究应用免疫组化方法分析CD 109在膀胱癌中表达的临床意义。156例尿路上皮癌组织中CD 109阳性率为69.9%，而7例正常膀胱上皮组织中CD 109均不表达。CD 109在非肌肉浸润性（pTa+ pT 1）或低级别（G1+G2）肿瘤中的表达显著高于肌肉浸润性（pT 2 -4）或高级别（G3）肿瘤，并且与癌症特异性生存相关。CD 109和磷酸化Smad 2的同时免疫染色显示两者之间的反向免疫反应性关系，表明CD 109抑制肿瘤组织中的TGF-β/Smad信号传导。有趣的是，发现CD 109在非浸润性尿路上皮癌的基底层中高度表达，并且表达模式与癌症干细胞的标志物CD 44相似。这些发现表明，CD 109参与膀胱肿瘤的发生，是癌症免疫治疗的潜在靶点。
Bladder cancer is one of the most common malignant diseases. Since a high-rate of recurrence is a serious problem for early stage urothelial carcinomas, new strategies for the management of recurrent urothelial carcinomas have been explored. CD109 is a glycosylphosphatidylinositol-anchored glycoprotein and is expressed in various cancer tissues, mainly squamous cell carcinomas. CD109 negatively controls transforming growth factor (TGF)-beta/Smad signaling in vitro. In this study, we analyzed the clinical significance of CD109 expression in bladder cancer using immunohistochemistry. Of 156 urothelial carcinoma tissues, 69.9% were positive for CD109, whereas CD109 was not expressed in seven normal bladder epithelia. CD109 expression was significantly higher in non-muscle-invasive (pTa+pT1) or low-grade (G1+G2) tumors than in muscle-invasive (pT2-4) or high-grade (G3) tumors, and was associated with cancer-specific survival. Simultaneous immunostaining of CD109 and phosphorylated Smad2 showed an inverse immunoreactivity relationship between the two, suggesting that CD109 inhibits TGF-beta/Smad signaling in tumor tissues. Interestingly, CD109 was found to be highly expressed in the basal layer of non-invasive urothelial carcinomas, and the expression pattern was similar to that of CD44, a marker of cancer stem cells. These findings suggest that CD109 is involved in bladder tumorigenesis and is a potential target for cancer immunotherapy.