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p53蛋白表达及肿瘤血管生成作为鼻咽癌患者的预后因素

Expression of p53 protein and tumor angiogenesis as prognostic factors in nasopharyngeal carcinoma patients.

作者信息

Rubio L, Burgos J S, Lopez-Guerrero J A, Morera C, Vera-Sempere F J

机构信息

Service of Pathology II, University Hospital La Fe, Medical School of Valencia University, Spain.

出版信息

Pathol Res Pract. 2002;198(2):97-102. doi: 10.1078/0344-0338-00193.

Abstract

The objective of this study was to evaluate the possible prognostic significance of p53 protein overexpression and tumor angiogenesis (TA) in nasopharyngeal carcinoma (NPC) patients, together with other clinicopathological variables. Forty-two NPC patients were evaluated in relation to survival. Nuclear p53 overexpression in neoplastic and endothelial cells was detected by immunohistochemistry (IHC) with the monoclonal antibody DO-7 and the polyclonal antibody against factor VIII-related antigen, respectively. Thereafter, we evaluated p53 cases in order to determine their nuclear immunoreactivity from negative (-) to positive (+, ++, +++). In addition, microvessels were counted in the most active areas of tumor neovascularization or hotspots using an image computer analyzer (MicroImage). A Cox multiple regression survival analysis was used to determine the best prognostic indicators in NPC patients. As a result, tumor microvessel count, considered as a continuous variable, was the most important independent prognostic indicator in relation to survival (p = 0.0273), with a relative risk of death of 2,4399 [95% confidence interval = 1.1051 ; 5.3871] associated with the highest microvessel counts. Moreover, the only clinicopathological variable that demonstrated prognostic value in a Cox multiple regression survival analysis was histological type (p = 0.05). In addition, we did not observe any statistical association between intratumoral microvessel density (IMD), clinicopathological variables and p53 protein expression.

摘要

本研究的目的是评估p53蛋白过表达和肿瘤血管生成(TA)在鼻咽癌(NPC)患者中与其他临床病理变量相关的可能预后意义。对42例NPC患者进行了生存评估。分别用单克隆抗体DO-7和抗VIII因子相关抗原的多克隆抗体通过免疫组织化学(IHC)检测肿瘤细胞和内皮细胞中的核p53过表达。此后,我们评估p53病例,以确定其核免疫反应性从阴性(-)到阳性(+、++、+++)。此外,使用图像计算机分析仪(MicroImage)在肿瘤新生血管形成最活跃的区域或热点区域计数微血管。采用Cox多元回归生存分析确定NPC患者的最佳预后指标。结果,被视为连续变量的肿瘤微血管计数是与生存相关的最重要的独立预后指标(p = 0.0273),微血管计数最高时死亡相对风险为2.4399[95%置信区间 = 1.1051;5.3871]。此外,在Cox多元回归生存分析中显示出预后价值的唯一临床病理变量是组织学类型(p = 0.05)。此外,我们未观察到肿瘤内微血管密度(IMD)、临床病理变量与p53蛋白表达之间存在任何统计学关联。

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