TLE3 is not a predictive biomarker for taxane sensitivity in the NCIC CTG MA.21 clinical trial.
TLE3 is not a predictive biomarker for taxane sensitivity in the NCIC CTG MA.21 clinical trial.
复制标题
DOI：
10.1038/bjc.2015.271
复制
发表时间：
2015-09-01
影响因子：
8.8
通讯作者：
NCIC CTG
中科院分区：
文献类型：
--
作者：
Bartlett JM;Nielsen TO;Gao D;Gelmon KA;Quintayo MA;Starczynski J;Han L;Burnell MJ;Levine MN;Chen BE;Shepherd LE;Chapman JW;NCIC CTG
TLE3是WNT信号传导途径下游的核转录抑制因子，已被假设为预测佐剂紫杉烷的益处。MA.21组织微阵列从2104名患者中的1097名（52%）构建。使用经验证的方法通过免疫组织化学进行TLE3染色。采用视觉和自动评分评估连续TLE3+（染色阳性细胞百分比）。主要目的是使用MA.21 EC/T和CEF组以及先前定义的在MA.21核心/肿瘤中30%的细胞染色阳性的临界点来测试TLE3对无复发生存期的预测作用。MA.21例患者通过视觉评分具有83.2%的TLE3阳性（TLE3+）肿瘤，通过自动图像分析具有80.6%的TLE3+，而先前观察到的TLE3+病例的比率为58.6%。TLE3表达与ER表达显著相关（91.2%的ER阳性肿瘤为TLE3 + P <0.0001）。在中位8年随访时，使用已确定的30%或探索性四分位数临界点，没有证据表明TLE3表达对紫杉烷获益具有预测作用。与预期相比，更多的MA.21患者肿瘤为TLE3+。预先规定的TLE3+临界点30%不能预测紫杉烷获益。TLE3表达并不代表乳腺癌中紫杉烷益处的可行生物标志物。
TLE3, a nuclear transcriptional repressor downstream of WNT signalling pathways, has been hypothesised as predictive of benefit from adjuvant taxane. MA.21 tissue microarrays were constructed from 1097 out of 2104 (52%) patients. TLE3 staining by immunohistochemistry used validated methodology. Continuous TLE3+ (percentage of cells staining positive) was assessed with both visual and automated scoring. The primary objective was to test the predictive effect of TLE3 on relapse-free survival using the MA.21 EC/T and CEF arms and the previously defined cut-point of 30% of cells staining positive in ⩾1 core/tumour. MA.21 patients had 83.2% TLE3 positive (TLE3+) tumours by visual score and 80.6% TLE3+ by automated image analysis while the previously observed rate of TLE3+ cases was 58.6%. TLE3 expression was significantly associated with ER expression (91.2% of ER-positive tumours were TLE3+ P<0.0001). At median 8-year follow-up, there was no evidence of a predictive effect of TLE3 expression with respect to taxane benefit using the established 30% or exploratory quartile cut-points. Proportionately more MA.21 patient tumours than expected were TLE3+. The pre-specified TLE3+ cut-point of 30% was not predictive of taxane benefit. TLE3 expression does not represent a viable biomarker for taxane benefit in breast cancer.