Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients
Gene expression patterns in formalin-fixed, paraffin-embedded core biopsies predict docetaxel chemosensitivity in breast cancer patients
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DOI：
10.1007/s10549-007-9590-z
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发表时间：
2008-03-01
影响因子：
3.8
通讯作者：
Shak, Steven
中科院分区：
文献类型：
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作者：
Chang, Jenny C.;Makris, Andreas;Shak, Steven
以前，我们已经确定了预测新辅助多西他赛反应的基因表达模式。其他研究已经证实，通过21基因RT-PCR测定的高复发评分（RS）预测预后更差，但对化疗的反应更好。我们研究了这21个基因和其他候选基因的肿瘤表达是否可以预测多西他赛的反应。在新辅助多西他赛治疗（4个周期，100 mg/m（2）q3 week）前，获得97例患者的核心活检。三个10 μ m的FFPE部分提交的192个基因，从我们以前的工作和文献中选择的定量RT-PCR检测。在97例患者中，81例（84%）有足够的浸润性癌症，80例（82%）有足够的RNA用于QRTPCR检测，72例（74%）有临床缓解数据。平均年龄为48.5岁，中位肿瘤大小为6 cm。临床完全缓解（CR）12例（17%），部分缓解41例（57%），疾病稳定17例（24%），疾病进展2例（3%）。CYBA等14个基因的表达与CR有显著相关性（P < 0.05）。CR与21基因检测中ER基因组的低表达和增殖基因组的高表达相关。值得注意的是，CR更可能与高RS（P = 0.008）。我们已经建立了多西他赛敏感性的分子特征。RT-PCR技术为使用少量常规处理的材料预测多西他赛化学敏感性提供了一个潜在的平台。
Previously, we had identified gene expression patterns that predicted response to neoadjuvant docetaxel. Other studies have validated that a high Recurrence Score (RS) by the 21-gene RT-PCR assay is predictive of worse prognosis but better response to chemotherapy. We investigated whether tumor expression of these 21 genes and other candidate genes can predict response to docetaxel. Core biopsies from 97 patients were obtained before treatment with neoadjuvant docetaxel (4 cycles, 100 mg/m(2) q3 weeks). Three 10-mu m FFPE sections were submitted for quantitative RT-PCR assays of 192 genes that were selected from our previous work and the literature. Of the 97 patients, 81 (84%) had sufficient invasive cancer, 80 (82%) had sufficient RNA for QRTPCR assay, and 72 (74%) had clinical response data. Mean age was 48.5 years, and the median tumor size was 6 cm. Clinical complete responses (CR) were observed in 12 (17%), partial responses in 41 (57%), stable disease in 17 (24%), and progressive disease in 2 patients (3%). A significant relationship (P < 0.05) between gene expression and CR was observed for 14 genes, including CYBA. CR was associated with lower expression of the ER gene group and higher expression of the proliferation gene group from the 21 gene assay. Of note, CR was more likely with a high RS (P = 0.008). We have established molecular profiles of sensitivity to docetaxel. RT-PCR technology provides a potential platform for a predictive test of docetaxel chemosensitivity using small amounts of routinely processed material.