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浸润性乳腺癌中ets-1蛋白表达的地形分布与肿瘤表型关系的研究。

Study of the topographic distribution of ets-1 protein expression in invasive breast carcinomas in relation to tumor phenotype.

作者信息

Mylona Eleni E, Alexandrou Paraskevi Th, Giannopoulou Ioanna A, Rafailidis Petros I, Markaki Sofia, Keramopoulos Antonios, Nakopoulou Lydia L

机构信息

Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias Str., Goudi, GR-115 27 Athens, Greece.

出版信息

Cancer Detect Prev. 2006;30(2):111-7. doi: 10.1016/j.cdp.2006.03.006. Epub 2006 May 2.

DOI:10.1016/j.cdp.2006.03.006
PMID:16632244
Abstract

BACKGROUND

Ets-1 is a transcription factor, implicated in the regulation of expression of various genes'. The aim of the present study was to investigate the expression of ets-1 protein in invasive breast carcinomas and its correlation with classic clinicopathological parameters, patients' survival and various biological markers.

METHODS

Immunohistochemistry was performed in paraffin-embedded tissue specimens from 149 invasive breast carcinomas to detect the proteins ets-1, p53, topoisomerase IIalpha, matrix metalloproteinase-7 (MMP-7) and urokinase-type plasminogen activator receptor (uPAR). Results were subjected to univariate and multivariate statistic analysis.

RESULTS

Ets-1 protein was detected in the 77.9% of the cases in the cytoplasm, in the 46.3% in the nucleus of the malignant cells, and in stromal fibroblasts as well. Cytoplasmic ets-1 was inversely correlated with nuclear and histologic grade of the tumor (p=0.004 and 0.033, respectively) and topoisomerase IIotaalpha (p=0.057), while nuclear ets-1 showed a positive association with p53 (p=0.002). Stromal ets-1 revealed a negative correlation with estrogen receptors (ER) (p=0.003) and a positive one with stromal uPAR and MMP-7 as well (p=0.048 and 0.066, respectively). The univariate statistic analysis showed nuclear ets-1 to be related to a shortened overall survival of the postmenopausal patients (p=0.032).

CONCLUSIONS

Ets-1 seems to be related to a different tumor phenotype according to its topographic distribution, with nuclear localization being associated with decreased apoptotic potential of the malignant cells through its relation to the mutant p53 protein, cytoplasmic being related to a favorable tumor phenotype and stromal ets-1 being related to tumor invasion.

摘要

背景

Ets-1是一种转录因子,参与多种基因表达的调控。本研究旨在探讨Ets-1蛋白在浸润性乳腺癌中的表达及其与经典临床病理参数、患者生存率和各种生物学标志物的相关性。

方法

对149例浸润性乳腺癌石蜡包埋组织标本进行免疫组织化学检测,以检测Ets-1、p53、拓扑异构酶IIα、基质金属蛋白酶-7(MMP-7)和尿激酶型纤溶酶原激活剂受体(uPAR)蛋白。对结果进行单因素和多因素统计分析。

结果

在77.9%的病例中,恶性细胞的细胞质中检测到Ets-1蛋白,46.3%在细胞核中检测到,在基质成纤维细胞中也有检测到。细胞质Ets-1与肿瘤的核分级和组织学分级呈负相关(分别为p = 0.004和0.033),与拓扑异构酶IIα呈负相关(p = 0.057),而细胞核Ets-1与p53呈正相关(p = 0.002)。基质Ets-1与雌激素受体(ER)呈负相关(p = 0.003),与基质uPAR和MMP-7也呈正相关(分别为p = 0.048和0.066)。单因素统计分析显示,细胞核Ets-1与绝经后患者的总生存期缩短有关(p = 0.032)。

结论

根据其拓扑分布,Ets-1似乎与不同的肿瘤表型相关,核定位通过与突变型p53蛋白的关系与恶性细胞凋亡潜能降低有关,细胞质定位与良好的肿瘤表型有关,基质Ets-1与肿瘤侵袭有关。

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