Reduced membranous and ectopic cytoplasmic expression of DSC2 in esophageal squamous cell carcinoma: an independent prognostic factor
Reduced membranous and ectopic cytoplasmic expression of DSC2 in esophageal squamous cell carcinoma: an independent prognostic factor
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DOI：
10.1016/j.humpath.2010.04.003
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发表时间：
2010-10-01
期刊：
影响因子：
3.3
通讯作者：
Xu, Li-Yan
中科院分区：
文献类型：
--
作者：
Fang, Wang-Kai;Gu, Wei;Xu, Li-Yan
Desmocollin 2 是一种桥粒成分，是一种关键的膜糖蛋白，与细胞间粘附和上皮正常组织结构的维持密切相关。探索桥粒胶蛋白表达与癌症之间联系的报告很有限。本研究的目的是调查食管鳞状细胞癌中桥粒胶蛋白 2 的表达，特别是确定桥粒胶蛋白 2 表达模式与临床参数的相关程度。采用免疫组织化学方法评估了 308 例食管鳞状细胞癌中 Desmocollin 2 的表达。进行蛋白质印迹和逆转录酶聚合酶链反应来表征桥粒胶蛋白 2 亚型的相对表达水平。结果表明，食管癌中桥粒胶蛋白 2 的表达在蛋白质和信使 RNA 水平上均显着降低，并且这种降低与较差的生存率相关 (P = .011)。桥粒胶蛋白2在正常食管上皮和高分化食管肿瘤中表达显着，但在低分化肿瘤标本中表达减少或不表达。此外，在 74.7% 的肿瘤组织中，桥粒胶蛋白 2 免疫反应性表现出异常的细胞质定位，与肿瘤分化差 (P < .001)、区域淋巴结转移 (P < .001)、病理肿瘤-淋巴结-转移阶段 (P < .001) 和预后不良 (P = .048) 相关。多因素分析显示桥粒胶蛋白2表达水平是食管鳞癌的独立预后因素。这些数据表明桥粒胶蛋白 2 参与食管肿瘤的转化和发展，并且桥粒胶蛋白 2 表达水平和细胞内定位可作为患者预后的预测因子。 (C) 2010 Elsevier Inc. 保留所有权利。
Desmocollin 2, a desmosomal component, is a key membrane glycoprotein critically involved in cell-cell adhesion and the maintenance of normal tissue architectures in epithelia. Reports exploring the link of desmocollin expression to cancers are limited. The aim of this study was to investigate the expression of desmocollin 2 in esophageal squamous cell carcinoma and, in particular, to determine the extent to which the patterns of desmocollin 2 expression correlated with the clinical parameters. Desmocollin 2 expression was evaluated in 308 cases of esophageal squamous cell carcinoma using immunohistochemistry. Western blotting and reverse transcriptase polymerase chain reaction were performed to characterize the relative expression levels of desmocollin 2 isoforms. The results indicated that desmocollin 2 expression was reduced significantly in esophageal cancer in both protein and messenger RNA levels and that this reduction was associated with poor survival (P = .011). The expression of desmocollin 2 was prominent in normal esophageal epithelia and highly differentiated esophageal tumors, but was reduced or absent in poorly differentiated tumor specimens. Furthermore, in 74.7% of tumor tissues, desmocollin 2 immunoreactivity displayed an abnormal cytoplasmic localization that was correlated with poor tumor differentiation (P < .001), regional lymph node metastasis (P < .001), pathologic tumor-node-metastasis stages (P < .001), and poor prognosis (P = .048). Multivariate analysis showed that desmocollin 2 expression level was an independent prognostic factor for esophageal squamous cell carcinoma. These data suggest that desmocollin 2 is involved in the transformation and development of esophageal tumors and that desmocollin 2 expression level and intracellular localization may serve as a predictor for patient outcomes. (C) 2010 Elsevier Inc. All rights reserved.