p53 Expression in node-positive breast cancer patients: results from the Cancer and Leukemia Group B 9344 Trial (159905).
p53 Expression in node-positive breast cancer patients: results from the Cancer and Leukemia Group B 9344 Trial (159905).
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DOI：
10.1158/1078-0432.ccr-11-0484
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发表时间：
2011-08-01
期刊：
影响因子：
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通讯作者：
Cancer and Leukemia Group B
中科院分区：
文献类型：
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作者：
Lara JF;Thor AD;Dressler LG;Broadwater G;Bleiweiss IJ;Edgerton S;Cowan D;Goldstein LJ;Martino S;Ingle JN;Henderson IC;Norton L;Winer EP;Hudis CA;Ellis MJ;Berry DA;Hayes DF;Cancer and Leukemia Group B
p53作为早期乳腺癌的预后和预测因子，结果喜忧参半。我们通过免疫组化研究了p53蛋白表达，在一项随机临床试验中，II期患者接受阿霉素和环磷酰胺联合或不联合紫杉醇的辅助治疗（CALGB 9344，INT 0148）。使用两种免疫组织化学抗体（DO 7和1801）在来自淋巴结阳性乳腺癌患者的福尔马林固定的石蜡包埋组织中评价上皮p53表达，这些患者被随机分配到4个周期的环磷酰胺和3种剂量的阿霉素（60、75或90 mg/m2）（AC）中的一种，并接受4个后续周期的紫杉醇（T）或不接受紫杉醇（T）。p53蛋白表达的预后和预测价值进行了评估，独立于治疗分配，递增剂量的阿霉素或添加T的RFS和OS的终点。1887的3121例患者标本治疗C9344获得，通过质量控制和p53表达进行了评价。mAbs 1801和D 07的表达分别为23%和27%，一致性为92%。在单变量分析中，p53阳性与任一抗体的OS较差相关，但仅单克隆抗体1801的p53染色的RFS显著较差。在多变量分析中，无论使用何种抗体，p53均不能预测多柔比星剂量递增或紫杉醇添加的RFS或OS。免疫组化法检测p53核染色与淋巴结阳性患者接受阿霉素辅助化疗后预后不良相关，但不是阿霉素剂量递增或紫杉醇加用后获益的有用预测因子。
p53 as a prognostic and predictive factor in early stage breast cancer, has had mixed results. We studied p53 protein expression, by immunohistochemistry, in a randomized clinical trial of stage II patients treated with adjuvant doxorubicin and cyclophosphamide with or without paclitaxel (CALGB 9344, INT0148). Epithelial p53 expression was evaluated using two immunohistochemical antibodies (DO7 and 1801) in formalin fixed, paraffin embedded tissue from patients with node positive breast cancer who were randomized to four cycles of cyclophosphamide and one of three doses of doxorubicin (60, 75, or 90 mg/m2) (AC) and to receive four subsequent cycles of paclitaxel (T) or not. Prognostic and predictive value of p53 protein expression was assessed, independent of treatment assignment, for escalating doses of doxorubicin or addition of T with endpoints of RFS and OS. 1887 of 3121 patient specimens treated on C9344 were obtained, passed quality control and evaluated for p53 expression. Expression was 23% and 27% for mAbs 1801 and D07 respectively, with 92% concordance. In univariate analysis, p53 positivity was associated with worse OS with either antibody, but only p53 staining with monoclonal antibody1801 had significantly worse RFS. In multivariate analysis, p53 was not predictive of RFS or OS from either doxorubicin dose escalation or addition of paclitaxel regardless of the antibody. Nuclear staining of p53 by immunohistochemistry is associated with worse prognosis in node positive patients treated with adjuvant doxorubicin-based chemotherapy, but is not a useful predictor of benefit from doxorubicin dose escalation or the addition of paclitaxel.