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葡萄糖转运蛋白-1在肾细胞癌中的表达及其与缺氧诱导因子-1α的相关性。

Glucose transporter-1 expression in renal cell carcinoma and its correlation with hypoxia inducible factor-1 alpha.

作者信息

Lidgren Anders, Bergh Anders, Grankvist Kjell, Rasmuson Torgny, Ljungberg Börje

机构信息

Department of Surgical and Perioperative Sciences, Umeå University, Umeå, Sweden.

出版信息

BJU Int. 2008 Feb;101(4):480-4. doi: 10.1111/j.1464-410X.2007.07238.x. Epub 2007 Oct 8.

Abstract

OBJECTIVE

To evaluate transcription factor hypoxia inducible factor-1 alpha (HIF-1 alpha) activity, by analysing a target gene for HIF-1 alpha, glucose transporter-1 (GLUT-1), using a tissue microarray (TMA) in different types of renal cell carcinoma (RCC, a tumour with a variable clinical course, partly due to angiogenic activity), as angiogenesis is important for tumour progression and metastatic spread, and is activated by hypoxia.

PATIENTS AND METHODS

GLUT-1 and HIF-1 alpha expressions were semiquantitatively analysed using immunohistological staining of a prepared TMA, using samples from 187 patients, including 148 with conventional, 26 with papillary and 13 with chromophobe RCC.

RESULTS

GLUT-1 staining was found mainly in the cytoplasm. The tumours were subdivided into GLUT -1(LOW) and GLUT-1(HIGH), based on staining intensity. There was a significant difference in GLUT-1 expression between RCC types (P < 0.05). In conventional RCC, GLUT-1 had no correlation with clinicopathological variables. By contrast there was a correlation with tumour stage in papillary RCC. There was an insignificant trend to better survival of patients with GLUT-1(LOW) expression in both conventional and papillary RCC. GLUT-1 correlated significantly (P = 0.008) with HIF-1 alpha.

CONCLUSIONS

Most patients with conventional RCC had GLUT-1(HIGH) staining and there was a significant correlation with HIF-1 alpha. In papillary RCC, GLUT-1 expression was associated with stage; GLUT-1 expression was significantly higher in conventional RCC than in papillary and chromophobe RCC. GLUT-1(LOW) in both papillary and conventional RCC appeared to correspond with a better prognosis.

摘要

目的

通过分析缺氧诱导因子-1α(HIF-1α)的靶基因葡萄糖转运蛋白-1(GLUT-1),利用组织微阵列(TMA)评估不同类型肾细胞癌(RCC,一种临床病程多变的肿瘤,部分原因是血管生成活性)中转录因子HIF-1α的活性,因为血管生成对肿瘤进展和转移扩散很重要,且由缺氧激活。

患者与方法

使用制备好的TMA进行免疫组织化学染色,对187例患者的样本进行GLUT-1和HIF-1α表达的半定量分析,其中包括148例传统型、26例乳头状和13例嫌色性RCC患者。

结果

GLUT-1染色主要位于细胞质中。根据染色强度将肿瘤分为GLUT-1(低表达)和GLUT-1(高表达)。不同类型RCC之间GLUT-1表达存在显著差异(P<0.05)。在传统型RCC中,GLUT-1与临床病理变量无相关性。相比之下,在乳头状RCC中与肿瘤分期相关。在传统型和乳头状RCC中,GLUT-1(低表达)患者的生存情况有不显著的更好趋势。GLUT-1与HIF-1α显著相关(P = 0.008)。

结论

大多数传统型RCC患者有GLUT-1(高表达)染色,且与HIF-1α显著相关。在乳头状RCC中,GLUT-1表达与分期相关;传统型RCC中GLUT-1表达显著高于乳头状和嫌色性RCC。乳头状和传统型RCC中的GLUT-1(低表达)似乎与较好的预后相关。

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