Vischioni B, van der Valk P, Span S W, Kruyt F A E, Rodriguez J A, Giaccone G
Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Ann Oncol. 2004 Nov;15(11):1654-60. doi: 10.1093/annonc/mdh436.
Expression of survivin, a member of the inhibitor of apoptosis protein family, is commonly detected in cancers but not in normal differentiated tissues. Survivin is usually localized in the cytoplasm of cancer cells, but nuclear localization has also been described, and we recently reported that survivin is a nuclear-cytoplasmic shuttling protein.
Fifty-three tumor specimens from patients with inoperable non-small-cell lung cancer (NSCLC) (55% stage IIIA, 17% stage IIIB and 28% stage IV) who underwent chemotherapy treatment were evaluated with immunohistochemistry for survivin expression and localization. These two sets of data were processed and tested for correlation with major patient characteristics, response to chemotherapy, and overall and relapse-free survival.
Survivin was present only in malignant tissues, and 47/53 (89%) of the specimens were positive. The overall median expression of tumor cells was 40%, and this value was used as a cut-off point for statistical analysis. By dichotomizing the specimens as expressing low or high levels of survivin, a significant association was seen between the expression of survivin and the histology of the tumors (P=0.020), squamous cell carcinoma being the histotype with lower levels of survivin expression. Three patterns of localization were observed: 42% of cases (22/53) showed reactivity confined to the nucleus, 17% (nine of 53) only in the cytoplasm and 30% (16/53) in both the nucleus and the cytoplasm. Interestingly, nuclear survivin levels predicted longer overall and relapse-free survival, in univariate and multivariate analyses. Expression and localization of survivin did not correlate with response to chemotherapy.
Our results indicate that differential localization of survivin may be a prognostic factor for NSCLC. Further studies are warranted.
凋亡抑制蛋白家族成员survivin的表达在癌症中普遍可检测到，但在正常分化组织中未被检测到。Survivin通常定位于癌细胞的细胞质中，但也有核定位的报道，并且我们最近报道survivin是一种核质穿梭蛋白。
对53例接受化疗的无法手术切除的非小细胞肺癌（NSCLC）患者（55%为IIIA期，17%为IIIB期，28%为IV期）的肿瘤标本进行免疫组织化学评估，以检测survivin的表达和定位。对这两组数据进行处理，并测试其与主要患者特征、化疗反应以及总生存期和无复发生存期的相关性。
Survivin仅存在于恶性组织中，53个标本中有47个（89%）呈阳性。肿瘤细胞的总体中位表达为40%，该值用作统计分析的截断点。将标本分为survivin表达水平低或高两组，发现survivin的表达与肿瘤组织学之间存在显著关联（P = 0.020），鳞状细胞癌是survivin表达水平较低的组织学类型。观察到三种定位模式：42%的病例（22/53）显示反应局限于细胞核，17%（53例中的9例）仅在细胞质中，30%（16/53）在细胞核和细胞质中均有反应。有趣的是，在单变量和多变量分析中，细胞核survivin水平预示着更长的总生存期和无复发生存期。Survivin的表达和定位与化疗反应无关。
我们的结果表明，survivin的差异定位可能是NSCLC的一个预后因素。有必要进行进一步研究。
