Provencio Mariano, Corbacho Cesar, Salas Clara, Millan Isabel, Espana Pilar, Bonilla Felix, Ramon Cajal Santiago
Department of Medical Oncology, University Hospital Puerta de Hierro, E-28035 Madrid, Spain.
Clin Cancer Res. 2003 Apr;9(4):1406-11.
Topoisomerase (Topo) II isoenzymes are the targets for drugs, such as epidophyllotoxins and doxorubicin. The aim of this study was to determine whether the expression of Topo IIalpha and Ki67 in advanced Hodgkin's disease (HD) played a role as a prognostic factor or predictor of response to treatment.
Forty-two patients who were homogeneously treated and had a long-term follow-up were selected for the study. Immunohistochemistry of paraffin-embedded tissue sections was performed. The effect of patient and tumor characteristics on failure-free survival (FFS) and overall survival were evaluated in a univariate analysis using the Cox proportional hazards model. The Cox model was also implemented in a multivariate analysis using stepwise selection.
Positive nuclear staining for Topo IIalpha in Reed-Stemberg or Reed-Stemberg variant cells was seen in 90% of HD cases, and coexpression of Ki67 and Topo IIalpha in 79%. No significant difference in the percentage of Topo IIalpha-positive cells was detected among histological HD subtypes. In the univariate analysis for FFS, the male gender, high lactate dehydrogenase, and Topo IIalpha < 30% were associated with more relapses. In the multivariate analysis for FFS, only Topo IIalpha < 30% was statistically associated with shorter FFS, with relative risk of 3 (95% confidence interval, 1.26-7.15; P = 0.013). In uni- and multivariate analyses for overall survival, only Topo IIalpha was associated with shorter survival.
Topo IIalpha expression could be useful in advanced HD to identify patients with a higher risk of relapse and lesser overall survival. It is of potential utility in the design of specific treatments.
拓扑异构酶（Topo）II 同工酶是表鬼臼毒素和阿霉素等药物的作用靶点。本研究的目的是确定 Topo IIα 和 Ki67 在晚期霍奇金淋巴瘤（HD）中的表达是否作为预后因素或治疗反应的预测指标。
选择 42 例接受同质治疗并进行长期随访的患者进行研究。对石蜡包埋的组织切片进行免疫组织化学检测。使用 Cox 比例风险模型在单变量分析中评估患者和肿瘤特征对无复发生存期（FFS）和总生存期的影响。Cox 模型也用于多变量分析中的逐步选择。
90%的 HD 病例中可见里德-斯腾伯格或里德-斯腾伯格变异细胞中 Topo IIα 呈阳性核染色，79%的病例中 Ki67 和 Topo IIα 共表达。在组织学 HD 亚型中，未检测到 Topo IIα 阳性细胞百分比的显著差异。在 FFS 的单变量分析中，男性、高乳酸脱氢酶以及 Topo IIα<30%与更多复发相关。在 FFS 的多变量分析中，只有 Topo IIα<30%与较短的 FFS 具有统计学相关性，相对风险为 3（95%置信区间，1.26 - 7.15；P = 0.013）。在总生存期的单变量和多变量分析中，只有 Topo IIα 与较短生存期相关。
Topo IIα 表达在晚期 HD 中可能有助于识别复发风险较高和总生存期较短的患者。它在特定治疗方案的设计中具有潜在用途。
Zotero 插件