Intense cytoplasmic ezrin immunoreactivity predicts poor survival in colorectal cancer

Intense cytoplasmic ezrin immunoreactivity predicts poor survival in colorectal cancer
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DOI:
10.1016/j.humpath.2008.04.020
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发表时间:
2008-12-01
期刊:
影响因子:
3.3
通讯作者:
Carpen, Otti
Carpen, Otti
中科院分区:
医学3区
文献类型:
--
作者:
Elzagheid, Adam;Korkefla, Eija;Carpen, Otti

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Ezrin是一种膜细胞骨架锚,在实验模型中,它调节肿瘤细胞的侵袭和转移能力。我们对74例晚期结直肠癌患者的ezrin进行了免疫组化分析,并将其与临床病理变量和疾病结局相关联。与正常结直肠上皮的主要膜性免疫反应性相反,ezrin在结直肠细胞中的表达通常是细胞质的。16.2%(12/74)的肿瘤ezrin呈阴性或弱染色,35.1%(26/74)为中度染色,48.6%(36/74)为强染色。结肠癌中表达较直肠癌强烈(P = 0.003)。ezrin表达增加与不良预后相关,即疾病特异性生存期缩短;阴性弱表达和强表达分别为48.3个月和36.6个月(P = 0.041), 36个月转移后生存期较短(P = 0.030);ezrin(阴性/弱)、ezrin(中度)、ezrin(强)组的转移率分别为58.3%、25.0%和18.4%。在单因素生存分析中,二分类(阴性/弱与中等/强)ezrin表达显著预测5年疾病特异性生存(P = 0.035)和5年转移(P = 0.18),但在多因素(Cox)分析中失去了这种预测能力。ezrin高表达与E-cadherin(细胞质)高表达、DNA非整倍性、胸腺苷合酶高表达相关(P = 0.046、P = 0.042、P = 0.046)。这些结果表明ezrin可能在结直肠癌的进展中起作用,并且ezrin的表达可能为预测结直肠癌的生物学行为提供有临床价值的信息。(C) 2008爱思唯尔公司版权所有。
Ezrin is a membrane cytoskeleton anchor, which, in experimental models, regulates tumor cell invasion and metastatic ability. We carried out immunohistochemical analysis of ezrin in 74 advanced colorectal cancer patients and correlated it to clinicopathologic variables and disease outcome. In contrast to the predominantly membraneous immunoreactivity of normal colorectal epithelium, ezrin expression in the colorectal cells was typically cytoplasmic. Altogether, 16.2% (12/74) of the tumors showed negative/weak ezrin staining, 35.1% (26/74) had moderate staining, and 48.6% (36/74) had intense staining. The expression was more intense in colon than in rectal carcinomas (P =.003). Increased ezrin expression was associated with adverse outcome, that is, shorter disease-specific survival; 48.3 months and 36.6 months for negative-weak versus intense expression (P =.041) as well as shorter survival with metastases at 36 months (P =.030); the metastases(36) rates in ezrin(neg/weak,) ezrin(moderate), ezrin(intense) are 58.3%, 25.0%, and 18.4%, respectively. In univariate survival analysis, dichotomized (negative/weak versus moderate/strong) ezrin expression significantly predicted both the 5-year disease specific survival (P =.035) and 5-year metastases (P =.0 18) but lost this predictive power in multivariate (Cox) analysis. High ezrin expression was also related to high E-cadherin (cytoplasmic) expression, DNA aneuploidy, and high thymidylate synthase expression (P =.046, P =.042, P =.046, respectively). These results suggest that ezrin may play a role in colorectal cancer progression and that ezrin expression might provide clinically valuable information in predicting the biological behavior of colorectal cancer. (C) 2008 Elsevier Inc. All rights reserved.