存活素蛋白的高表达水平可独立预测接受透明细胞肾细胞癌手术患者的不良预后。

High expression levels of survivin protein independently predict a poor outcome for patients who undergo surgery for clear cell renal cell carcinoma.

作者信息

Parker Alexander S, Kosari Farhad, Lohse Christine M, Houston Thompson R, Kwon Eugene D, Murphy Linda, Riehle Darren L, Blute Michael L, Leibovich Bradley C, Vasmatzis George, Cheville John C

机构信息

Department of Urology, Mayo Clinic College of Medicine, Jacksonville, Florida, USA.

出版信息

Cancer. 2006 Jul 1;107(1):37-45. doi: 10.1002/cncr.21952.

DOI:10.1002/cncr.21952

PMID:16736510

Abstract

BACKGROUND

In a previous study of gene array data, the authors identified survivin as a candidate marker of aggressiveness in clear cell renal cell carcinoma (ccRCC). What remained in question was whether survivin expression at the protein level is an independent predictor of disease progression and cancer-specific survival.

METHODS

Between 1990 and 1994, 312 patients underwent nephrectomy for ccRCC at Mayo Clinic Rochester and had paraffin tissue available. The authors performed immunohistochemistry with antisurvivin antibody, quantitated the expression by using an image-analysis system, and analyzed the association of survivin expression with disease progression and cancer-specific survival.

RESULTS

Within the cohort, 97 patients (31.1%) had high levels of survivin expression. Patients who had high survivin expression levels were at significantly increased risk of death from RCC compared with patients who had low expression levels (risk ratio [RR], 5.3; 95% confidence interval [95% CI], 3.5-7.9). The 5-year cancer-specific survival rate was 43.0% for patients with high survivin expression and 87.2% for patients with low survivin expression. In multivariate analysis, survivin expression remained associated with death from RCC even after adjusting for the Eastern Cooperative Oncology Group performance status; 2002 Tumor, Lymph Node, Metastases (TNM) stage groupings and nuclear grade (RR, 2.4; 95%CI, 1.5-3.8); and the Mayo Clinic composite TNM stage groupings, tumor size, nuclear grade, and tumor necrosis (SSIGN) score (RR, 1.8; 95%CI, 1.1-2.9). Among 273 patients who had localized ccRCC, survivin expression was associated significantly with cancer progression (RR, 3.9; 95%CI, 2.4-6.2).

CONCLUSIONS

Survivin expression is an independent predictor of ccRCC progression and death from RCC. Thus, survivin has the potential to offer additional prognostic information and to provide a novel target for the development of new adjuvant therapies.

摘要

背景

在之前一项基因阵列数据研究中，作者将生存素确定为肾透明细胞癌（ccRCC）侵袭性的候选标志物。尚待解决的问题是，生存素蛋白水平的表达是否为疾病进展和癌症特异性生存的独立预测指标。

方法

1990年至1994年间，312例患者在梅奥诊所罗切斯特院区因ccRCC接受了肾切除术，且有石蜡组织可用。作者用抗生存素抗体进行免疫组织化学，使用图像分析系统对表达进行定量，并分析生存素表达与疾病进展和癌症特异性生存的关联。

结果

在该队列中，97例患者（31.1%）生存素表达水平高。与低表达水平患者相比，生存素表达水平高的患者死于RCC的风险显著增加（风险比[RR]，5.3；95%置信区间[95%CI]，3.5 - 7.9）。生存素高表达患者的5年癌症特异性生存率为43.0%，低表达患者为87.2%。在多变量分析中，即使在调整东部肿瘤协作组体能状态、2002年肿瘤、淋巴结、转移（TNM）分期分组和核分级（RR，2.4；95%CI，1.5 - 3.8）以及梅奥诊所综合TNM分期分组、肿瘤大小、核分级和肿瘤坏死（SSIGN）评分后，生存素表达仍与死于RCC相关（RR，1.8；95%CI，1.1 - 2.9）。在273例局限性ccRCC患者中，生存素表达与癌症进展显著相关（RR，3.9；95%CI，2.4 - 6.2）。