Higher expression of topoisomerase II alpha is an independent marker of increased risk of cancer-specific death in patients with clear cell renal cell carcinoma.
Higher expression of topoisomerase II alpha is an independent marker of increased risk of cancer-specific death in patients with clear cell renal cell carcinoma.
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DOI：
10.1016/j.eururo.2013.12.017
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发表时间：
2014-11
期刊：
影响因子：
23.4
通讯作者：
Leibovich, Bradley C.
中科院分区：
文献类型：
--
作者：
Parker, Alexander S.;Eckel-Passow, Jeanette E.;Serie, Daniel;Hilton, Tracy;Parasramka, Mansi;Joseph, Richard W.;Wu, Kevin J.;Cheville, John C.;Leibovich, Bradley C.
透明细胞肾细胞癌（ccRCC）患者预后的基于肿瘤的生物标志物仍然有限，特别是对于那些低风险疾病的患者。IIa型拓扑异构酶（TOPOIIa）是一种众所周知的DNA复制生物标志物和抗肿瘤药物的靶标，但尚未被评估为ccRCC结局的生物标志物。评估ccRCC中TOPOIIa表达与术后癌症特异性死亡风险的关系。两项独立队列研究在美国三级转诊泌尿外科实践中进行了研究。我们确定了1378例（分析）和279例（验证）患者的队列，这些患者接受了临床局限性ccRCC的肾切除术，并有石蜡肿瘤组织。使用免疫组织化学评估TOPOIIa的表达，并以每平方毫米阳性细胞的数量进行评分。我们的主要终点是癌症特异性生存（CSS）。我们将TOPOIIa表达作为一个连续变量进行评估，并将其分为低和高。对于与CSS的关联，我们使用Kaplan-Meier曲线和Cox回归模型。在这两个队列中，TOPOIIa高表达的患者发生ccRCC死亡的可能性大约是低表达患者的三倍（风险比[HR]: 2.75； 95%可信区间[CI]， 2.12-3.56; p = 1.79E-14和HR: 3.45; 95% CI, 1.34-8.88; p = 0.0104）。侵袭性病理特征的多变量调整并不能解释这些关联，分层分析表明，根据梅奥临床分期、大小、分级和坏死评分，这种关联在低风险疾病患者中更为明显。在接受ccRCC手术的患者中，较高的TOPOIIa表达与癌症死亡风险增加独立相关，并且在低风险患者中具有显著的预后价值。对ccRCC中TOPOIIa的评估为指导ccRCC患者的术后监测提供了机会，并为设计更有针对性的临床试验和新的治疗策略提供了信息。
Tumor-based biomarkers of outcome for patients with clear cell renal cell carcinoma (ccRCC) remain limited, especially for those with low-risk disease. Type IIa topoisomerase (TOPOIIa) is a well-known biomarker of DNA replication and a target for antineoplastic agents, but it has not been evaluated as a biomarker of ccRCC outcome. To evaluate the association of TOPOIIa expression in ccRCC and risk of cancer-specific death following surgery. Two independent cohort studies were studied in tertiary referral urology practices in the United States. We identified cohorts of 1378 (analytic) and 279 (validation) patients who underwent nephrectomy for clinically localized ccRCC and had paraffin tumor tissue available. TOPOIIa expression was assessed using immunohistochemistry and scored as the number of positive cells per square millimeter. Our primary end point was cancer-specific survival (CSS). We evaluated TOPOIIa expression as a continuous variable and dichotomized as low versus high. For associations with CSS, we used Kaplan-Meier curves and Cox regression models. In both cohorts, patients who had high TOPOIIa expression were approximately three times more likely to experience ccRCC death than those with low expression (hazard ratio [HR]: 2.75; 95% confidence interval [CI], 2.12–3.56; p = 1.79E-14 and HR: 3.45; 95% CI, 1.34–8.88; p = 0.0104, respectively). Multivariable adjustment for pathologic features of aggressiveness did not explain these associations, and stratified analysis suggests that the association is more pronounced among patients with low-risk disease as defined by the Mayo Clinic stage, size, grade, and necrosis score. Higher TOPOIIa expression is independently associated with increased risk of cancer death among patients undergoing surgery for ccRCC, and the prognostic value is pronounced among patients with low-risk disease. Evaluation of TOPOIIa in ccRCC provides the opportunity to help guide postsurgical surveillance for ccRCC patients as well as inform the design of more targeted clinical trials and novel treatment strategies.
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影响因子：
6.6
作者：
Fujii, Yasuhisa;Saito, Kazutaka;Kihara, Kazunori
通讯作者：
Kihara, Kazunori
DOI：
10.1038/nrc2608
发表时间：
2009-05
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
--
影响因子：
23.4
作者：
Sun, Maxine;Thuret, Rodolphe;Karakiewicz, Pierre I.
通讯作者：
Karakiewicz, Pierre I.
DOI：
10.1016/s1078-1439(02)00205-3
发表时间：
2003-01-01
影响因子：
2.7
作者：
Leslie, JA;Prihoda, T;Thompson, IM
通讯作者：
Thompson, IM
影响因子：
2.4
作者：
Cho, Eunyoung;Adami, Hans-Olov;Lindblad, Per
通讯作者：
Lindblad, Per