Poikonen P, Sjöström J, Amini R-M, Villman K, Ahlgren J, Blomqvist C
Department of Oncology, Helsinki University Central Hospital, PO Box 180, 00029 HUS Helsinki, Finland.
Br J Cancer. 2005 Sep 5;93(5):515-9. doi: 10.1038/sj.bjc.6602735.
We wanted to study cyclin A as a marker for prognosis and chemotherapy response. A total of 283 women with metastatic breast cancer were initially enrolled in a randomised multicentre trial comparing docetaxel to sequential methotrexate-fluorouracil (MF) in advanced breast cancer after anthracycline failure. Paraffin-embedded blocks of the primary tumour were available for 96 patients (34%). The proportion of cells expressing cyclin A was determined by immunohistochemistry using a mouse monoclonal antibody to human cyclin A. Response evaluation was performed according to WHO recommendations. The median cyclin A positivity of tumour cells was 14.5% (range 1.2-45.0). Cyclin A correlated statistically significantly to all other tested proliferation markers (mitotic count, histological grade and Ki-67). A high cyclin A correlated significantly to a shorter time to first relapse, risk ratio (RR) 1.94 (95% CI 1.24-3.03) and survival from diagnosis, RR 2.49 (95% CI 1.45-4.29), cutoff point for high/low proliferation group 10.5%. Cyclin A did not correlate to chemotherapy response or survival after anthracycline, docetaxel or MF therapy. Of all tumour biological factors tested (mitotic count, histological grade and Ki-67), cyclin A seemed to have the strongest prognostic value. Cyclin A is a good marker for tumour proliferation and prognosis in breast cancer. In the present study, cyclin A did not predict chemotherapy response.
我们希望研究细胞周期蛋白A作为预后和化疗反应标志物的情况。共有283例转移性乳腺癌女性最初被纳入一项随机多中心试验，该试验比较了多西他赛与序贯甲氨蝶呤-氟尿嘧啶（MF）用于蒽环类药物治疗失败后的晚期乳腺癌。96例患者（34%）有原发性肿瘤的石蜡包埋块。使用抗人细胞周期蛋白A的小鼠单克隆抗体通过免疫组织化学法测定表达细胞周期蛋白A的细胞比例。根据世界卫生组织的建议进行疗效评估。肿瘤细胞的细胞周期蛋白A阳性率中位数为14.5%（范围1.2 - 45.0）。细胞周期蛋白A与所有其他检测的增殖标志物（有丝分裂计数、组织学分级和Ki-67）在统计学上显著相关。高细胞周期蛋白A水平与首次复发时间缩短显著相关，风险比（RR）为1.94（95%可信区间1.24 - 3.03），与诊断后的生存期相关，RR为2.49（95%可信区间1.45 - 4.29），高/低增殖组的分界点为10.5%。细胞周期蛋白A与蒽环类药物、多西他赛或MF治疗后的化疗反应或生存期无关。在所有检测的肿瘤生物学因素（有丝分裂计数、组织学分级和Ki-67）中，细胞周期蛋白A似乎具有最强的预后价值。细胞周期蛋白A是乳腺癌肿瘤增殖和预后的良好标志物。在本研究中，细胞周期蛋白A不能预测化疗反应。
