Mesh : Adult Aged Aged, 80 and over Biomarkers / metabolism Breast Neoplasms / metabolism mortality pathology Carcinoma, Ductal, Breast / metabolism mortality pathology Carcinoma, Lobular / metabolism mortality pathology Female Humans Immunohistochemistry Middle Aged Neoplasm Invasiveness Phenotype Postmenopause Premenopause Proto-Oncogene Protein c-ets-1 / metabolism Survival Analysis

来  源:   DOI:10.1016/j.cdp.2006.03.006

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,与各种基因表达的调节有关。本研究的目的是探讨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的相关性。患者的存活率和各种生物学标志物。
方法:在149例浸润性乳腺癌的石蜡包埋组织标本中进行免疫组织化学,以检测蛋白ets-1,p53,拓扑异构酶IIalpha,基质金属蛋白酶-7(MMP-7)和尿激酶型纤溶酶原激活物受体(uPAR)。结果进行单因素和多因素统计分析。
结果:在77.9%的病例中在胞浆中检测到Ets-1蛋白,在恶性细胞核中的46.3%,以及基质成纤维细胞。细胞质ets-1与肿瘤的核和组织学分级(分别为p=0.004和0.033)和拓扑异构酶IIotaalpha(p=0.057)呈负相关,而核ets-1与p53呈正相关(p=0.002)。基质ets-1显示与雌激素受体(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)。单变量统计分析显示,nuclearets-1与绝经后患者的总生存期缩短有关(p=0.032)。
结论:根据地形分布,Ets-1似乎与不同的肿瘤表型有关,核定位通过与突变型p53蛋白的关系与恶性细胞的凋亡潜能降低有关,细胞质与有利的肿瘤表型相关,基质ets-1与肿瘤侵袭相关。
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