Chemotherapy-induced apoptosis and Bcl-2 levels correlate with breast cancer response to chemotherapy
Chemotherapy-induced apoptosis and Bcl-2 levels correlate with breast cancer response to chemotherapy
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DOI：
10.1097/00130404-200301000-00007
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发表时间：
2003-01-01
期刊：
影响因子：
2.2
通讯作者：
Sahin, AA
中科院分区：
文献类型：
--
作者：
Buchholz, TA;Davis, DW;Sahin, AA
目的：细胞凋亡与乳腺癌化疗反应的相关性尚不清楚。我们研究了化疗后肿瘤细胞凋亡和 Bcl-2 表达的变化是否与乳腺癌治疗的反应相关。 患者和方法：在两个或三个时间点对 25 个乳腺癌原发性肿瘤进行连续核心活检：治疗前 (N = 24) 和第一个化疗周期开始后约 24 小时 (N = 22) 和/或 48 小时 (N = 19)。通过使用荧光末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸缺口末端标记 (TUNEL) 染色来量化细胞凋亡水平，并通过半定量免疫组织化学测定来测量 Bcl-2 和 Bax。所有计算的P值都是两侧的。结果：33个病理完全缓解或残留病灶<1 cm的肿瘤（中位，22％；范围，6％-51％）48小时时的细胞凋亡水平显着高于残留病灶> 1 cm的肿瘤（中位，7％；范围，1％-36％）；曼惠特尼测试。这种差异也存在于接受多西紫杉醇/阿霉素化疗的 16 个肿瘤亚组中（分别为 25% 和 4%）。化疗后 Bcl-2 表达相对于治疗前样本表达的降低也与疾病反应相关。具体而言，Bcl-2 降低的 9 个肿瘤中有 3 个出现病理学完全缓解，而 Bcl-2 水平稳定的 15 个肿瘤中有 0 个达到病理学完全缓解（Fisher 精确检验）。 Bax 的连续测量与反应之间没有关系。讨论：这些数据表明细胞凋亡可能在确定乳腺癌对化疗的反应中发挥重要作用，并且治疗诱导的细胞凋亡水平作为预测标记可能具有一定的价值。
PURPOSE: The relevance of apoptosis to breast cancer response to chemotherapy is unclear. We investigated whether changes in tumor cell apoptosis and Bcl-2 expression immediately after chemotherapy correlated with response to breast cancer treatment.PATIENTS AND METHODS: Serial core biopsies of 25 breast cancer primary tumors were performed at either two or three time points: before treatment (N = 24) and approximately 24 hours (N = 22) and/or 48 hours (N = 19) after the initiation of the first cycle of chemotherapy. Apoptosis levels were quantified by use of a fluorescent terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling (TUNEL) stain, and Bcl-2 and Bax were measured by semiquantitative immunohistochemical assays. All calculated P values were two sided.RESULTS: The apoptosis level at 48 hours was significantly higher in the 33 tumors with pathological complete response or < 1 cm of residualdisease (median, 22%; range, 6%-51%) than in the tumors with > 1 cm residual disease (median, 7%; range, 1%-36%); Mann-Whitney test. This difference was also present in the subgroup of 16 tumors treated with docetaxel/doxorubicin chemotherapy (25% vs 4%, respectively). A decrease in Bcl-2 expression after chemotherapy relative to the expression from the pretreatment sample also correlated with disease response. Specifically, three of the nine tumors with a decrease in Bcl-2 had a pathological complete response, compared with 0 of the 15 tumors with stable levels of Bcl-2 (Fisher's exact test). There was no relationship between serial measurements of Bax and response.DISCUSSION: These data suggest that apoptosis may play an important role in determining breast cancer response to chemotherapy and that the level of treatment-induced apoptosis may have some value as a predictive marker.