Bria E, Visca P, Novelli F, Casini B, Diodoro M G, Perrone-Donnorso R, Botti C, Sperduti I, Facciolo F, Milella M, Cecere F L, Cognetti F, Mottolese M
Medical Oncology, Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144 Rome, Italy.
Eur J Surg Oncol. 2008 May;34(5):593-8. doi: 10.1016/j.ejso.2007.06.002. Epub 2007 Aug 10.
Survivin is a member of the inhibitors of apoptosis (IAP) gene family that acts through pathways different from those involving the bcl-2 family. Largely undetectable in normal adult tissues, survivin is deregulated in most human cancers including non-small-cell lung cancer (NSCLC) and may represent a tumor marker with prognostic and therapeutic implications. Aim of our study was to determine the prognostic role of survivin as an apoptosis-related biomarker in a series of resected NSCLC patients.
A retrospective series of resected NSCLC patients were retrieved from the files of the Regina Elena National Cancer Institute. Survivin was detected by immunohistochemistry (IHC) using a polyclonal antibody. Survivin displayed two kinds of immunoreactivity: (i) a diffuse cytoplasmic staining and (ii) a distinct nuclear staining. A score-scale to distinguish positive (score 1-2) vs. negative (score 0) pattern was applied. Clinical and biological (nuclear and cytoplasmic survivin staining) covariables were screened for a prognostic relationship with overall survival (OS) and disease-free survival (DFS) into the univariate and multivariate analyses.
Data referring to 116 NSCLC patients who underwent surgery for stage I-IIIA NSCLC were collected. Multivariate analyses identified tumor size, nodal status and nuclear, but not cytoplasmic, expression of survivin as significant independent predictors of OS, with a hazard ratio of 2.40 (95% CI 1.44, 3.99, p=0.001), 2.03 (95% CI 1.26, 3.26, p=0.003) and 1.83 (95% CI 1.01, 3.30, p=0.044), respectively. Median OS for nuclear survivin positive (score 1-2) and negative (score 0) patients were 23 months (95% CI 15, 31) and 36 months (95% CI 1, 76), respectively (p=0.01); five-year survival for score 1-2 and score 0 patients were 20% and 44.5%, respectively. Conversely, no significant impact on survival is found when patients are stratified according to cytoplasmic survivin expression.
Data presented herein open the issue that prognosis of stage I-IIIA NSCLC can be linked to the cellular pattern of distribution of survivin.
生存素是凋亡抑制蛋白（IAP）基因家族的成员，其作用途径不同于涉及bcl-2家族的途径。在正常成人组织中基本检测不到生存素，在包括非小细胞肺癌（NSCLC）在内的大多数人类癌症中，生存素的表达失调，它可能是一种具有预后和治疗意义的肿瘤标志物。本研究的目的是确定生存素作为凋亡相关生物标志物在一系列接受手术切除的NSCLC患者中的预后作用。
从 Regina Elena 国家癌症研究所的档案中检索出一系列接受手术切除的 NSCLC 患者。使用多克隆抗体通过免疫组织化学（IHC）检测生存素。生存素表现出两种免疫反应性：（i）弥漫性细胞质染色和（ii）明显的细胞核染色。应用评分量表来区分阳性（评分1 - 2）与阴性（评分0）模式。在单变量和多变量分析中，筛选临床和生物学（细胞核和细胞质生存素染色）协变量与总生存期（OS）和无病生存期（DFS）的预后关系。
收集了116例接受I - IIIA期NSCLC手术的患者的数据。多变量分析确定肿瘤大小、淋巴结状态以及生存素的细胞核而非细胞质表达是OS的显著独立预测因素，风险比分别为2.40（95%CI 1.44, 3.99, p = 0.001）、2.03（95%CI 1.26, 3.26, p = 0.003）和1.83（95%CI 1.01, 3.30, p = 0.044）。细胞核生存素阳性（评分1 - 2）和阴性（评分0）患者的中位OS分别为23个月（95%CI 15, 31）和36个月（95%CI 1, 76）（p = 0.01）；评分1 - 2和评分0患者的五年生存率分别为20%和44.5%。相反，根据细胞质生存素表达对患者进行分层时，未发现对生存有显著影响。
本文所呈现的数据提出了一个问题，即I - IIIA期NSCLC的预后可能与生存素的细胞分布模式有关。
