The apoptosis regulators p53, bax and PUMA: Relationship and impact on outcome in early stage (FIGO I-II) ovarian carcinoma after post-surgical taxane-based treatment
The apoptosis regulators p53, bax and PUMA: Relationship and impact on outcome in early stage (FIGO I-II) ovarian carcinoma after post-surgical taxane-based treatment
复制标题
凋亡调节因子 p53、bax 和 PUMA：早期（FIGO I-II）卵巢癌术后以类固醇为基础的治疗中的关系及其对预后的影响
DOI：
10.3892/or.2011.1578
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发表时间：
2012-03-01
期刊：
影响因子：
4.2
通讯作者：
Seidal, T.
中科院分区：
文献类型：
--
作者：
Skirnisdottir, I.;Seidal, T.
本研究的目的是评估凋亡调节因子p53、bax和p53 A对105例FIGO I-II期上皮性卵巢癌患者复发和无病生存（DFS）的预后影响，所有患者均接受术后铂类紫杉烷化疗。采用组织芯片和免疫组化技术检测p53、bax和p53/bax/bax/bax/p53的表达。p53阳性率为24%，bax阳性率为83%，而p53蛋白强阳性率为43%。bax表达与肿瘤分级有关（P=0.029）。bax阳性表达与肿瘤组织中CITRA的强阳性表达有关（P=0.004）。p53、bax或bax A单独或合并状态（p53 bax、p53 bax A和bax bax A）与年龄、组织病理学亚型、浆液性/非浆液性肿瘤或初次手术分期程序类型无关。在生存分析中，p53阳性肿瘤（P=0.014）和伴随的p53阳性和弱PUMA阳性肿瘤（P=0.015）与较短的DFS显著相关。同时p53阴性和bax阳性的肿瘤与较长的生存期显著相关（P=0.019）。Logistic回归分析显示FIGO分期（OR=6.0）和p53状态（OR=4.1）是肿瘤复发的预测因素，多因素考克斯回归分析显示FIGO分期和p53状态是肿瘤复发的独立预后因素（HR=2.4）。在一项单独的考克斯多变量回归分析中，p53 bax状态（HR=2.2）是DFS的独立预后因素。p53 β A状态（HR=0.4）不是一个独立的预后因素，但有临界意义（P=0.07）。我们的研究结果表明，FIGO分期和p53状态是独立的复发和生存预后因素的预测因素。此外，在本研究中，p53 Bax状态是生存的独立预后因素。
The objective of this study was to evaluate the prognostic effect of the apoptosis regulators p53, bax and PUMA for recurrent disease and disease-free survival (DFS) in a series of 105 patients in FIGO-stages I-II with epithelial ovarian cancer, all treated with post-surgical platinum-taxane chemotherapy. For the detection of positivity of the biological markers p53, bax and PUMA the techniques of tissue microarrays and immunohistochemistry (IHC) were used. In tumors the frequency of p53 positivity was 24%, that of bax positivity was 83%, and strong positivity was found for PUMA (43%). The bax status was related to tumor grade (P=0.029). Positive staining for bax was related to strong positivity of PUMA in the tumors (P=0.004). The p53, bax or PUMA status alone or concomitant (p53 bax, p53 PUMA and bax PUMA) were not related to age, histopathological subtype, serous/non-serous tumors or type of the staging procedure at primary surgery. In survival analysis p53-positive tumors (P=0.014) and concomitant p53-positive and weak PUMA-positive tumors (P=0.015) were significantly correlated with shorter DFS. Concomitant p53-negative and bax-positive tumors were significantly correlated with longer survival (P=0.019). FIGO-stage (OR=6.0) and p53 status (OR=4.1) were predictive factors for tumor recurrence in logistic regression analysis and independent prognostic factors (HR=2.4 for both) in multivariate Cox regression analysis. In a separate Cox multivariate regression analysis the p53 bax status (HR=2.2) was an independent prognostic factor for DFS. The p53 PUMA status (HR=0.4) was not an independent prognostic factor, however, a borderline significance (P=0.07) was noted. Our results indicate that FIGO stage and p53 status alone were independent predictive factors for recurrence and prognostic factors for survival. Furthermore, p53 bax status was an independent prognostic factor for survival in this study.