GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER-negative breast cancer
GSTP1 expression predicts poor pathological complete response to neoadjuvant chemotherapy in ER-negative breast cancer
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DOI：
10.1111/j.1349-7006.2012.02231.x
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发表时间：
2012-05-01
期刊：
影响因子：
5.7
通讯作者：
Noguchi, Shinzaburo
中科院分区：
文献类型：
--
作者：
Miyake, Tomohiro;Nakayama, Takahiro;Noguchi, Shinzaburo
本研究旨在探讨乳腺癌组织中谷胱甘肽S转移酶P1的表达与新辅助紫杉醇耐药和5-氟尿嘧啶/表阿霉素/环磷酰胺耐药的关系。并探讨了GSTP1基因表达和GSTP1启动子高甲基化与固有亚型的关系。在这项研究中，分析了接受P-FEC新辅助治疗的原发性乳腺癌患者(n=类似于123例，IIIII期)。肿瘤标本在P-FEC术前经真空辅助核芯活检获得。用免疫组织化学方法检测GSTP1的表达，用亚硫酸氢法测定启动子甲基化指数(MI)，用DNA芯片检测固有亚型。雌激素受体(ER)阴性组的病理完全缓解率(80.0%)明显高于阳性组(30.6%)(P<0.009)，而ER阳性组的病理完全缓解率则无显著差异(P>0.267)。多因素分析显示，在ER阴性肿瘤中，GSTP1PCR值是唯一的预测因子(P=0.013)。腔A、腔B和富含HER2的肿瘤的GSTP1阳性率显著低于基底样瘤(P类似于=类似于0.002，P类似于
The purpose of the present study was to investigate the association of glutathione S-transferase P1 (GSTP1) expression with resistance to neoadjuvant paclitaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide (P-FEC) in human breast cancers. The relationship of GSTP1 expression and GSTP1 promoter hypermethylation with intrinsic subtypes was also investigated. In this study, primary breast cancer patients (n similar to=similar to 123, stage IIIII) treated with neoadjuvant P-FEC were analyzed. Tumor samples were obtained by vacuum-assisted core biopsy before P-FEC. GSTP1 expression was determined using immunohistochemistry, GSTP1 promoter methylation index (MI) using bisulfite methylation assay and intrinsic subtypes using DNA microarray. The pathological complete response (pCR) rate was significantly higher in GSTP1-negative tumors (80.0%) than GSTP1-positive tumors (30.6%) (P similar to=similar to 0.009) among estrogen receptor (ER)-negative tumors but not among ER-positive tumors (P similar to=similar to 0.267). Multivariate analysis showed that GSTP1 was the only predictive factor for pCR (P similar to=similar to 0.013) among ER-negative tumors. Luminal A, luminal B and HER2-enriched tumors showed a significantly lower GSTP1 positivity than basal-like tumors (P similar to=similar to 0.002, P similar to