title: CXCR7 expression is associated with disease-free and disease-specific survival in cervical cancer patients.
abstract: BACKGROUND
  The CXC chemokine receptor (CXCR)7 is involved in tumour development and metastases formation. The aim of the present study was to determine protein expression of CXCR7, its putative co-receptors epidermal growth factor receptor (EGFR) and CXCR4, its predominant ligand CXCL12, their co-dependency and their association with survival in cervical cancer patients.
  
  
  METHODS
  CXC chemokine receptor 7, EGFR, CXCR4 and CXCL12 expression were determined immunohistochemically in 103 paraffin-embedded, cervical cancers. Subsequently, associations with patient characteristics were assessed and survival analyses were performed.
  
  
  RESULTS
  CXC chemokine receptor 7 was expressed by 43% of tumour specimens, in a large majority of cases together with either EGFR or CXCR4 (double positive), or both (triple positive). The CXCR7 expression was associated with tumour size (P=0.013), lymph node metastasis (P=0.001) and EGFR expression (P=0.009). CXC chemokine receptor 7 was independently associated with disease-free survival (hazard ratio (HR)=4.3, 95% confidence intervals (CI) 1.7-11.0, P=0.002), and strongly associated with disease-specific survival (HR=3.9, 95% CI 1.5-10.2, P=0.005).
  
  
  CONCLUSIONS
  CXC chemokine receptor 7 expression predicts poor disease-free and disease-specific survival in cervical cancer patients, and might be a promising new therapeutic marker. In a large majority of cases, CXCR7 is co-expressed with CXCR4 and/or EGFR, supporting the hypothesis that these receptors assist in CXCR7 signal transduction.
authors.affiliation: Department of Pathology, Leiden University Medical Center, RC Leiden, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Schrevel
authors.forename: R
authors.initials: R
authors.lastname: Karim
authors.forename: N T
authors.initials: NT
authors.lastname: ter Haar
authors.forename: S H
authors.initials: SH
authors.lastname: van der Burg
authors.forename: J B M Z
authors.initials: JB
authors.lastname: Trimbos
authors.forename: G J
authors.initials: GJ
authors.lastname: Fleuren
authors.forename: A
authors.initials: A
authors.lastname: Gorter
authors.forename: E S
authors.initials: ES
authors.lastname: Jordanova
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D002584:Cervix Uteri / Q000378:metabolism / Q000473:pathology; D054377:Chemokine CXCL12 / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D008207:Lymphatic Metastasis; D008875:Middle Aged; D011379:Prognosis; D054387:Receptors, CXCR / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D055815:Young Adult
chemical_list: C501896:ACKR3 protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D054387:Receptors, CXCR; D019718:Receptors, CXCR4; C512478:EGFR protein, human; D066246:ErbB Receptors