MacGrogan G, Rudolph P, Mascarel Id I de, Mauriac L, Durand M, Avril A, Dilhuydy J M, Robert J, Mathoulin-Pélissier S, Picot V, Floquet A, Sierankowski G, Coindre J M
Department of Pathology, Institut Bergonié, 229 Cours de l'Argonne, 33076 Bordeaux cedex France.
Br J Cancer. 2003 Aug 18;89(4):666-71. doi: 10.1038/sj.bjc.6601185.
The alpha isoform of Topoisomerase IIalpha (Topo IIalpha) is a proliferation marker as well as a target for several chemotherapeutic agents such as anthracyclines. In vitro studies have demonstrated the relationship between the Topo IIalpha expression level and chemosensitivity of target cancer cells. To verify this effect in vivo, we selected 125 patients presenting with T(2)>3 cm and T(3) N(0-1) M(0) breast tumours who were treated by six cycles of primary chemotherapy, including epirubicin before any surgery. Therapy response was assessed by clinical and X-ray mammogram measurements of tumour shrinkage. The pretherapeutic core biopsies were immunostained with a monoclonal antibody (Ki-S7) against Topo IIalpha. Ki-S7 positivity ranged from 0 to 50% (median, 15%). A high percentage of Ki-S7-positive cells (>15%) was associated with tumour regression under chemotherapy (OR=2.88, CI: 1.3-6.4, P=0.004). Ki-S7 further emerged as an independent predictor of tumour regression (OR=3.34, CI: 1.41-7.93, P=0.006), together with tumour size of less than 40 mm (OR=3.82, CI: 1.58-9.25, P=0.002) and negative oestrogen receptor (ER) status (OR=3.35, CI: 1.43-7.86, P=0.005), in a multivariate analysis including tumour size, SBR grade, ER and PR status, Ki-67, p53 and Her-2/neu. Our clinical results confirm in vitro data on the relationship between Topo IIalpha expression and tumour chemosensitivity and thus may have important practical implications.
拓扑异构酶IIα（Topo IIα）的α亚型既是一种增殖标志物，也是几种化疗药物（如蒽环类药物）的作用靶点。体外研究已经证实了Topo IIα表达水平与靶癌细胞化疗敏感性之间的关系。为了在体内验证这种效应，我们选取了125例患有T(2)>3 cm和T(3) N(0 - 1) M(0)期乳腺肿瘤的患者，这些患者在任何手术前均接受了六个周期的以表柔比星为主的新辅助化疗。通过临床检查和乳腺X线摄影测量肿瘤缩小情况来评估治疗反应。治疗前的核心活检组织用抗Topo IIα的单克隆抗体（Ki - S7）进行免疫染色。Ki - S7阳性率范围为0%至50%（中位数为15%）。化疗后Ki - S7阳性细胞比例高（>15%）与肿瘤退缩相关（OR = 2.88，CI：1.3 - 6.4，P = 0.004）。在一项包括肿瘤大小、SBR分级、雌激素受体（ER）和孕激素受体（PR）状态、Ki - 67、p53和Her - 2/neu的多因素分析中，Ki - S7与肿瘤大小小于40 mm（OR = 3.82，CI：1.58 - 9.25，P = 0.002）以及雌激素受体（ER）阴性状态（OR = 3.35，CI：1.43 - 7.86，P = 0.005）一起，进一步成为肿瘤退缩的独立预测因素（OR = 3.34，CI：1.41 - 7.93，P = 0.006）。我们的临床结果证实了体外研究中关于Topo IIα表达与肿瘤化疗敏感性之间关系的数据，因此可能具有重要的实际意义。
