title: Decreased expression of C-erbB-2 and CXCR4 in breast cancer after primary chemotherapy.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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).
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Shi-Xin
authors.initials: SX
authors.lastname: Yang
authors.forename: Wings T Y
authors.initials: WT
authors.lastname: Loo
authors.forename: Louis W C
authors.initials: LW
authors.lastname: Chow
authors.forename: Xin-hua
authors.initials: XH
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhan
authors.forename: Lin-Jun
authors.initials: LJ
authors.lastname: Fan
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Qing-liang
authors.initials: QL
authors.lastname: Wang
authors.forename: Hua-Liang
authors.initials: HL
authors.lastname: Xiao
authors.forename: Jin-Long
authors.initials: JL
authors.lastname: Wu
authors.forename: Xiu-wu
authors.initials: XW
authors.lastname: Bian
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D013194:Staining and Labeling; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D047628:Estrogen Receptor alpha; D000090063:Proto-Oncogene Mas; D018719:Erb-b2 Receptor Tyrosine Kinases; D019718:Receptors, CXCR4; C527276:CXCR4 protein, human; C506487:ESR1 protein, human; C000715470:MAS1 protein, human; C508053:ERBB2 protein, human