Apolinario R M, van der Valk P, de Jong J S, Deville W, van Ark-Otte J, Dingemans A M, van Mourik J C, Postmus P E, Pinedo H M, Giaccone G
Department of Medical Oncology, Vrije Universiteit and University Hospital, Amsterdam, the Netherlands.
J Clin Oncol. 1997 Jun;15(6):2456-66. doi: 10.1200/JCO.1997.15.6.2456.
To assess the prognostic value of p53, bcl-2, bax, and neovascularization in radically resected non-small-cell lung cancer (NSCLC) patients.
Tumors 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.
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-/PAb1801+ tumors as those 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 those 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 (> or = 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.
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.
评估p53、bcl-2、bax以及新生血管形成在接受根治性切除的非小细胞肺癌（NSCLC）患者中的预后价值。
采用免疫组织化学方法评估116例患者肿瘤组织中p53（DO7和PAb1081）、bcl-2的表达以及微血管密度（CD-31）的定量情况。此外，对61例I期肿瘤组织评估bax的表达。将每种标志物的表达中位数水平作为截断点。
p53与任何患者或肿瘤特征均无相关性，而bcl-2在鳞状细胞癌中表达较高（P <.001）。bax表达与男性性别（P =.006）及腺癌类型（P =.0013）显著相关。用一种单克隆抗体（MoAb）评估的p53状态不能预测生存情况；然而，用两种MoAb获得的染色结果联合分析发现，DO7 - /PAb1801 +肿瘤的预后最差。bcl-2表达与I期患者的较长生存期相关（P =.0169）。在I期患者及整个研究队列中，与两种癌蛋白的其他组合相比，p53 +（PAb1801）/bcl-2 -联合表达组的生存期最差（P =.034）。单独的bax表达对I期患者的生存无影响，但bax + /bcl-2 -肿瘤患者的预后最差（与bax + /bcl-2 +相比，P =.02）。肿瘤新生血管形成与其他因素无关，仅在II期患者中，CD-31 +肿瘤患者的生存期短于CD-31 -肿瘤患者（P =.0283）。通过对所有患者进行多因素分析，p53 + /bcl-2 -肿瘤表达的存在以及肿瘤直径较大（≥4cm）是生存期较短的独立预后因素。对于I期患者，只有bax + /bcl-2 -肿瘤表达的存在对生存有显著负面影响。
新的生物学标志物（如参与凋亡途径的标志物）之间的相互作用和调节是复杂的。与仅研究其中一种标志物相比，几种标志物表达的联合分析可能提供更有价值的信息。p53染色的预后影响因抗体的选择而异，并且bcl-2 -与p53 +（PAb1801）联合或与bax +联合对I期NSCLC患者的生存影响最差。
