Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
J Transl Med. 2012 Sep 19;10 Suppl 1(Suppl 1):S3. doi: 10.1186/1479-5876-10-S1-S3.
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.
原癌基因 erbB-2（HER-2/neu，c-erbB-2）、CXC 趋化因子受体 4（CXCR4）、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）等生物分子标志物在接受新辅助化疗后发生改变，这些蛋白表达的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。采用免疫组织化学（IHC）法在全组织切片和组织微阵列（TMA）上检测 C-erbB-2、CXCR4 和 ER-α 的表达。采用 IHC 法在 TMA 上检测 PCNA、TopoII、P-gp 和 GST 的表达。另一方面，通过 Western blot 分析对 16 对接受新辅助化疗的原发性乳腺癌患者的术前核心活检进行 CXCR4、C-erbB-2 和 ER-α 的表达检测。最终手术标本取自接受新辅助化疗并获得部分缓解（PR）的乳腺癌患者。
本研究数据表明，患者在接受全组织切片和 TMA 新辅助化疗后，C-erbB-2、CXCR4 和 ER-α 的水平降低。PCNA 水平在接受新辅助化疗后下调，TopoII、P-gp 和 GST 未见明显变化。Western blot 检测也显示，C-erbB-2、CXCR4 和 ER-α 水平在接受新辅助化疗后也下调。此外，在全组织切片和 TMA 上，Pearson 卡方分析显示 C-erbB-2 和 CXCR4 的变化表达与新辅助化疗的病理变化趋势相关。
本研究表明，乳腺癌患者接受新辅助系统治疗后，C-erbB2、ER-α 和 CXCR4 的表达降低。C-erbB-2 和 CXCR4 的下调表达可能是化疗的一种新机制；这些客观标志物的变化可能有助于评估乳腺癌新辅助化疗的临床反应。
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