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原发性肾细胞癌内p27(Kip1)表达的异质性、其浸润边缘和瘤旁肾实质与病理及预后特征的相关性。

Heterogeneous p27(Kip1) expression within primary renal cell cancers, their invasive margins and peritumoral renal parenchyma correlation with pathological and prognostic features.

作者信息

Merseburger A S, Serth J, von der Heyde E, Kobierski A, Wegener U, Mengel M, Jonas U, Kuczyk M

机构信息

Department of Urology, Eberhard Karls University Tübingen, Germany.

出版信息

Urol Int. 2007;79(2):164-9. doi: 10.1159/000106332.

Abstract

INTRODUCTION

The expression of the negative cell cycle regulator p27(Kip1) is frequently found to be deregulated in various human cancer types. Whether expression of p27(Kip1) can be used as prognostically relevant biological variables for renal cell cancer patients still remains to be clarified. Therefore, in the present investigation the expression within different tissue areas obtained from renal cell carcinomas was determined.

PATIENTS AND METHODS

For analysis of p27(Kip1) in 420 tumor nephrectomy specimens obtained from 420 consecutively included patients, tissue microarrays were used comprising of 1,260 tissue samples each obtained from the tumor itself, the invasive front as well as non-malignant surrounding parenchyma. A sufficient follow-up after surgical therapy was available in 251 cases.

RESULTS

In univariate survival analysis, decreased expression of p27(Kip1) within tissue cores obtained from the invasion front was significantly correlated with the patients' disease-specific long-term survival (p = 0.02, log-rank test). In contrast, expression of p27(Kip1) protein within the primary tumors was not identified to reveal any prognostically important information. In Cox regression analysis, histological stage and grade (p < 0.01), the presence of regional lymph node (p < 0.01) or distant metastases at the time of surgery (p < 0.01) as well as decreased expression of p27(Kip1) (p = 0.04) within the invasion front tissue samples independently predicted the disease-specific long-term survival following surgery.

CONCLUSION

Our analysis demonstrated that p27(Kip1) is heterogeneously expressed in renal cell carcinomas. Moreover, the result of the present study supports the prognostic value of p27(Kip1) protein expression for patients diagnosed with renal cell carcinoma.

摘要

引言

在多种人类癌症类型中,经常发现负性细胞周期调节因子p27(Kip1)的表达失调。p27(Kip1)的表达是否可作为肾细胞癌患者预后相关的生物学变量仍有待阐明。因此,在本研究中,我们测定了肾细胞癌不同组织区域内的表达情况。

患者与方法

为分析420例连续纳入患者的肿瘤肾切除标本中的p27(Kip1),使用了组织微阵列,其由1260个组织样本组成,每个样本分别取自肿瘤本身、浸润前沿以及非恶性周围实质。251例患者术后有足够的随访资料。

结果

在单因素生存分析中,取自浸润前沿的组织芯内p27(Kip1)表达降低与患者疾病特异性长期生存显著相关(p = 0.02,对数秩检验)。相比之下,未发现原发肿瘤内p27(Kip1)蛋白表达能揭示任何预后重要信息。在Cox回归分析中,组织学分期和分级(p < 0.01)、手术时区域淋巴结转移(p < 0.01)或远处转移(p < 0.01)以及浸润前沿组织样本中p27(Kip1)表达降低(p = 0.04)独立预测术后疾病特异性长期生存。

结论

我们的分析表明,p27(Kip1)在肾细胞癌中呈异质性表达。此外,本研究结果支持p27(Kip1)蛋白表达对肾细胞癌患者的预后价值。

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