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CD133干性标志物的细胞质表达与透明细胞肾细胞癌的肿瘤侵袭性相关。

Cytoplasmic expression of CD133 stemness marker is associated with tumor aggressiveness in clear cell renal cell carcinoma.

作者信息

Saeednejad Zanjani Leili, Madjd Zahra, Abolhasani Maryam, Andersson Yvonne, Rasti Arezoo, Shariftabrizi Ahmad, Asgari Mojgan

机构信息

Oncopathology Research Centre, Iran University of Medical Sciences (IUMS), Tehran, Iran.

Oncopathology Research Centre, Iran University of Medical Sciences (IUMS), Tehran, Iran; Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran.

出版信息

Exp Mol Pathol. 2017 Oct;103(2):218-228. doi: 10.1016/j.yexmp.2017.10.001. Epub 2017 Oct 16.

DOI:10.1016/j.yexmp.2017.10.001
PMID:29050853
Abstract

Prominin-1 (CD133) is one of the most commonly used markers for cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. However, the clinical and prognostic significance of CSCs in renal cell carcinoma (RCC) remains unclear. The aim of this study was to investigate the expression patterns and prognostic significance of the cancer stem cell marker CD133 in different histological subtypes of RCC. CD133 expression was evaluated using immunohistochemistry in 193 well-defined renal tumor samples on tissue microarrays, including 136 (70.5%) clear cell renal cell carcinomas (CCRCCs), 26 (13.5%) papillary RCCs, and 31 (16.1%) chromophobe RCCs. The association between CD133 expression and clinicopathological features as well as the survival outcomes was determined. There was a statistically significant difference between CD133 expression among the different RCC subtypes. In CCRCC, higher cytoplasmic expression of CD133 was significantly associated with increase in grade, stage, microvascular invasion (MVI) and lymph node invasion (LNI), while no association was found with the membranous expression. Moreover, on multivariate analysis, TNM stage and nuclear grade were independent prognostic factors for overall survival (OS) in cytoplasmic expression. We showed that higher cytoplasmic CD133 expression was associated with more aggressive tumor behavior and more advanced disease in CCRCC but not in the other examined subtypes. Our results demonstrated that higher cytoplasmic CD133 expression is clinically significant in CCRCC and is associated with increased tumor aggressiveness and is useful for predicting cancer progression.

摘要

促红细胞生成素-1(CD133)是癌症干细胞(CSCs)最常用的标志物之一,其特征在于具有自我更新和致瘤性。然而,CSCs在肾细胞癌(RCC)中的临床和预后意义仍不清楚。本研究的目的是探讨癌症干细胞标志物CD133在不同组织学亚型RCC中的表达模式和预后意义。采用免疫组织化学方法对组织芯片上193例明确诊断的肾肿瘤样本中的CD133表达进行评估,其中包括136例(70.5%)透明细胞肾细胞癌(CCRCCs)、26例(13.5%)乳头状RCCs和31例(16.1%)嫌色性RCCs。确定CD133表达与临床病理特征以及生存结果之间的关联。不同RCC亚型之间的CD133表达存在统计学显著差异。在CCRCC中,CD133较高的细胞质表达与分级、分期、微血管侵犯(MVI)和淋巴结侵犯(LNI)增加显著相关,而与膜性表达无关。此外,多因素分析显示,TNM分期和核分级是细胞质表达中总生存(OS)的独立预后因素。我们发现,在CCRCC中较高的细胞质CD133表达与更具侵袭性的肿瘤行为和更晚期疾病相关,但在其他检测的亚型中并非如此。我们的结果表明,较高的细胞质CD133表达在CCRCC中具有临床意义,与肿瘤侵袭性增加相关,有助于预测癌症进展。

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