title: Chemokine receptors in advanced breast cancer: differential expression in metastatic disease sites with diagnostic and therapeutic implications.
abstract: BACKGROUND
  We investigated the expression of CXCR4, CCR7, estrogen receptor (ER), progesterone receptor (PR) and HER2-neu in human metastatic breast cancers to determine whether these biological biomarkers were preferentially expressed in any organ-specific metastases.
  
  
  METHODS
  CXCR4, CCR7, ER, PR and HER2-neu expression levels were evaluated by immunohistochemical staining using paraffin-embedded tissue sections of metastatic breast cancers (n = 41) obtained by either diagnostic biopsy or surgical resection.
  
  
  RESULTS
  The metastatic sites included the following: bone (n = 15), brain (n = 14), lung (n = 6), liver (n = 2), and omental metastases (n = 2). CXCR4 was expressed in 41% of cases, CCR7 expression was demonstrated in 10%, and HER2-neu overexpression was present in 27%. CXCR4 was more likely to be expressed in bone metastases than visceral metastases (67% versus 26%, P = 0.020). Visceral sites demonstrated a lower rate of CXCR4 positivity (33% and 23%, respectively, for lung and brain metastases). Similarly, CCR7 was more likely to be found in bone metastases than visceral sites (27% versus 0%, P = 0.037).
  
  
  CONCLUSIONS
  These results indicate that CXCR4 can contribute to the homing of breast cancer cells to the bone. This finding might have important clinical implications since patients with metastatic bone disease may achieve the highest benefit from a CXCR4-targeted therapy.
authors.affiliation: Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX 77230, USA.
authors.forename: N
authors.initials: N
authors.lastname: Cabioglu
authors.forename: A A
authors.initials: AA
authors.lastname: Sahin
authors.forename: P
authors.initials: P
authors.lastname: Morandi
authors.forename: F
authors.initials: F
authors.lastname: Meric-Bernstam
authors.forename: R
authors.initials: R
authors.lastname: Islam
authors.forename: H Y
authors.initials: HY
authors.lastname: Lin
authors.forename: C D
authors.initials: CD
authors.lastname: Bucana
authors.forename: A M
authors.initials: AM
authors.lastname: Gonzalez-Angulo
authors.forename: G N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: M
authors.initials: M
authors.lastname: Cristofanilli
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D054400:Receptors, CCR7 / Q000096:biosynthesis; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C515370:CCR7 protein, human; C527276:CXCR4 protein, human