Lodge A J, Hall A G, Reid M M, McIntosh G G, Steward M, Anderson J J, Horne C H, Angus B
Department of Pathology, University of Newcastle, Queen Victoria Road, Newcastle upon Tyne, NE2 4HH, UK.
J Clin Pathol. 2001 Jan;54(1):31-6. doi: 10.1136/jcp.54.1.31.
BACKGROUND/AIMS: Many regimens used in the treatment of childhood acute lymphoblastic leukaemia (ALL) include Daunorubicin or Etoposide, which act as topoisomerase poisons. It has been suggested that there may be a relation between topoisomerase expression and response to topoisomerase poisons, based mainly on results from in vitro studies. Therefore, the aim of this study was to investigate this relation in a clinical setting and determine whether topoisomerase II alpha and II beta might be of predictive value in ALL.
Cellular expression of topoisomerases II alpha and II beta was assessed in 177 cases of ALL by immunohistochemistry using monoclonal antibodies to the two enzymes. The percentages of cell nuclei showing positive staining for topoisomerase II alpha and II beta expression were assessed.
Taking the series as a whole, a clear separation of survival curves was seen with the established prognostic markers white blood cell (WBC) count, CD10 status, and sex. However, topoisomerase II alpha and II beta expression showed no relation to survival. No association was found between the topoisomerases and the prognostic markers CD10 and WBC count; however, topoisomerase II alpha expression was found to be related to sex, with expression being lower in girls (p = 0.002).
These results suggest that the response to topoisomerase poisons cannot be predicted by the assessment of topoisomerase II alpha and II beta expression as defined by immunohistochemistry.
背景/目的：许多用于治疗儿童急性淋巴细胞白血病（ALL）的方案都包含柔红霉素或依托泊苷，它们作为拓扑异构酶毒物发挥作用。主要基于体外研究结果，有人提出拓扑异构酶表达与对拓扑异构酶毒物的反应之间可能存在关联。因此，本研究的目的是在临床环境中研究这种关联，并确定拓扑异构酶IIα和IIβ在ALL中是否可能具有预测价值。
通过使用针对这两种酶的单克隆抗体进行免疫组织化学，评估了177例ALL患者中拓扑异构酶IIα和IIβ的细胞表达。评估了显示拓扑异构酶IIα和IIβ表达阳性染色的细胞核百分比。
就整个系列而言，已确立的预后标志物白细胞（WBC）计数、CD10状态和性别可使生存曲线明显分开。然而，拓扑异构酶IIα和IIβ的表达与生存无相关性。未发现拓扑异构酶与预后标志物CD10和WBC计数之间存在关联；但是，发现拓扑异构酶IIα的表达与性别有关，女孩中的表达较低（p = 0.002）。
这些结果表明，通过免疫组织化学定义的拓扑异构酶IIα和IIβ表达评估无法预测对拓扑异构酶毒物的反应。
