Prognostic value of the expression of p53, bcl-2, and bax oncoproteins, and neovascularization in patients with radically resected non-small-cell lung cancer
Prognostic value of the expression of p53, bcl-2, and bax oncoproteins, and neovascularization in patients with radically resected non-small-cell lung cancer
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DOI：
10.1200/jco.1997.15.6.2456
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发表时间：
1997-06-01
影响因子：
45.3
通讯作者：
Giaccone, G
中科院分区：
文献类型：
--
作者：
Apolinario, RM;vanderValk, P;Giaccone, G
目的：方法：采用免疫组化方法检测116例胃癌患者的p53（DO 7和PAb 1081）、bcl-2表达及微血管密度（CD-31）。此外，在61个I期肿瘤中评估了bax的表达。每种标志物的表达水平的中位数被用作截止点。p53与任何患者或肿瘤特征无关，而bcl-2在鳞状细胞癌中表达较高bax表达与男性显著相关（P <0.001）（P = .006）和腺癌型（P = 0.0013），用一种单克隆抗体（MoAb）评估的p53状态不能预测生存;然而，用两种MoAb获得的染色结果的组合鉴定了具有最差预后的DO 7（-）/PAb 1801（+）肿瘤，bcl-2表达与I期患者的生存期延长相关（P = 0.0169）。p53（+）（PAb 1801）/bcl-2（-）联合表达组在I期患者中生存率最低（P = 0.034），在整个系列中，与两种癌蛋白的其他组合相比，单独的bax表达对I期患者的生存没有影响，bax（+）/bcl-2（-）组预后最差（P = 0.02）。肿瘤新生血管与其他因素无关，CD-31（+）肿瘤患者的生存期短于仅在II期的CD-31（-）肿瘤患者（P = 0.0283）。多因素分析显示，p53（+）/ bcl-2（-）表达和肿瘤直径大于或等于4cm是影响生存期的独立预后因素。对于I期，只有bax（+）/ bcl-2（-）表达对生存率有显著的负面影响。结论：新的生物学标志物，如参与凋亡途径的生物学标志物，相互作用和调节是复杂的。将其中几种表达方式结合起来，可能比只研究一种表达方式提供更有价值的信息。p53染色的预后影响根据抗体的选择而变化，bcl-2（-）与p53（+）（PAb 1801）或与bax（+）的组合对I期NSCLC患者的生存率具有最差的影响，（C）1997由美国临床肿瘤学会（American Society of Clinical Oncology）。
Purpose: To assess the prognostic value of p53, bcl-2, bax, and neovascularizaPatients and Methods: Turners from 116 patients were assessed by immunohistochemistry for expression of p53 (DO7 and PAb1081), bcl-2, and the quantification of microvessel density (CD-31). In addition, the expression of bax was assessed in 61 stage I tumors. The median levels of expression of each marker were used as cutoff points.Results: p53 was not correlated to any patient or tumor characteristic, whereas bcl-2 showed higher expression in squamous cell carcinomas (P < .001), bax expression was significantly related with male sex (P = .006) and adenocarcinoma type (P = .0013), p53 status, assessed with one monoclonal antibody (MoAb), was not predictive for survival; however, the combination of staining results obtained with two MoAbs identified the DO7(-)/PAb 1801(+) tumors as chose with the worst prognosis, bcl-2 expression was associated with longer survival in stage I patients (P = .0169). The combined group expressing p53(+)(PAb1801)/bcl-2(-) had the worst survival in stage I patients (P = .034) and in the whole series in comparison with the other combinations of the two oncoproteins bax expression alone had no influence on survival of stage I patients, but patients with bax(+)/bcl-2(-) tumors had the worst prognosis (P = .02 in comparison with bax(+)/bcl-2(+)). Tumor neovascularization was not related with other factors, and patients with CD-31(+) tumors had a shorter survival duration than these with CD-31(-) tumors only in stage II (P = .0283). By multivariate analysis including all patients, the presence of p53(+)/ bcl-2(-) tumor expression and large tumor diameter (greater than or equal to 4cm) were independent prognostic factors for shorter survival duration. For stage I, only the presence of bax(+)/ bcl-2(-) tumor expression had a significant negative influence on survival,Conclusion: The interaction and the regulation of new biologic markers, such as those involved in the apoptotic pathway, are complex. Combinations of the expression of several of them may give more valuable information than the study of just one. Prognostic influence of p53 staining varied depending on the choice of antibody and the combination of bcl-2(-) together with p53(+) (PAb1801) or with bax(+) had the worst influence on survival for patients with stage I NSCLC, (C) 1997 by American Society of Clinical Oncology.