Decreased expression of C-erbB-2 and CXCR4 in breast cancer after primary chemotherapy.
Decreased expression of C-erbB-2 and CXCR4 in breast cancer after primary chemotherapy.
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DOI：
10.1186/1479-5876-10-s1-s3
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发表时间：
2012-09-19
影响因子：
7.4
通讯作者：
Jiang J
中科院分区：
文献类型：
--
作者：
Yang SX;Loo WT;Chow LW;Yang XH;Zhan Y;Fan LJ;Zhang F;Chen L;Wang QL;Xiao HL;Wu JL;Bian XW;Jiang J
原癌基因erbB-2等生物分子标志物（HER-2/neu，c-erbB-2），CXC趋化因子受体4（CXCR 4），雌激素受体（ER），增殖细胞核抗原（PCNA），DNA拓扑异构酶II（topo II），P-糖蛋白（P-gp）和谷胱甘肽S-转移酶（GST）观察新化疗后的变化，以及这些蛋白表达变化是否与化疗反应相关。本研究纳入了64例接受新辅助化疗的原发性乳腺癌患者。采用免疫组化（IHC）法检测C-erbB-2、CXCR 4和ER-α在全组织切片和组织芯片上的表达。免疫组化法检测PCNA、Topo Ⅱ、P-gp和GST。同时对16对新鲜的术前穿刺活检标本进行Western blot检测CXCR 4、C-erbB-2和ER-α的表达。最终的手术标本来自接受新辅助化疗并获得部分缓解（PR）的乳腺癌患者。我们的数据表明，患者在接受全组织切片和TMA的新辅助化疗后，C-erbB-2，CXCR 4和ER-α的水平降低。新辅助化疗后PCNA表达明显下调，Topo Ⅱ、P-gp、GST表达无明显变化。免疫印迹法检测C-erbB-2、CXCR 4和ER-α水平在新辅助化疗后也明显下调。Pearson卡方分析显示，C-erbB-2和CXCR 4表达的变化与新辅助化疗后全组织切片和TMAs的病理变化有相关性。我们的研究表明，乳腺癌患者接受新辅助全身治疗后，观察到C-erbB 2、ER-α和CXCR 4的表达下降。c-erbB-2和CXCR 4表达下调可能是乳腺癌新辅助化疗的一个新机制，这些客观指标的变化可能有助于评价乳腺癌新辅助化疗的临床疗效。
Biological molecular markers such as proto-oncogene erbB-2 (HER-2/neu, c-erbB-2), the CXC chemokine receptor 4 (CXCR4), estrogen receptor (ER), Proliferating Cell Nuclear Antigen (PCNA), DNA topoisomerase II (topo II), P-glycoprotein (P-gp) and glutathione S-transferase (GST) were observed for changes after administration of neochemotherapy and whether these protein expression changes were correlated with response to chemotherapy. Sixty-four patients with primary breast cancer who had undergone neo-adjuvant chemotherapy were enrolled in the present study. The expressions of C-erbB-2, CXCR4 and ER-α were measured by immunohistochemistry (IHC) on full tissue sections and on tissue microarrays (TMAs). PCNA, TopoII, P-gp and GST were measured by IHC on TMAs. On the other hand, CXCR4, C-erbB-2 and ER-α expressions were detected using western blot analysis to 16 pairs of fresh preoperative core biopsies. The final surgical specimens were obtained from patients with breast carcinoma who received neo-adjuvant chemotherapy and obtained a partial response (PR). Our data demonstrated that the levels of C-erbB-2, CXCR4 and ER-α in patients decreased after they received neo-adjuvant chemotherapy on full tissue sections and on TMAs. The PCNA level was down-regulated after receiving neo-adjuvant chemotherapy, and no significant change was observed for TopoII, P-gp and GST. The levels of C-erbB-2, CXCR4 and ER-α were also down-regulated after neo-adjuvant chemotherapy was administered, as detected by western blot. In addition, the change expressions of C-erbB-2 and CXCR4 in specimens tended to be correlated with pathological change to neo-adjuvant chemotherapy on full tissue sections and on TMAs in a Pearson chi-square analysis. As demonstrated in our study, after breast cancer patients were treated with neo-adjuvant systemic therapy, decreased expressions of C-erbB2, ER-α and CXCR4 were observed. Down-regulated expressions of c-erbB-2 and CXCR4 may be a novel mechanism of chemotherapy; the changes of these objective markers may be useful in evaluating the clinical response of neo-adjuvant chemotherapy in breast cancer.