title: CXCR4 overexpression is associated with poor outcome in females diagnosed with stage IV non-small cell lung cancer.
abstract: BACKGROUND
  It has been proposed that the chemokine receptor, CXCR4, and its ligand, stromal cell-derived factor-1 (SDF-1), play a critical role in organ-specific tumor metastasis. High CXCR4 expression in resected non-small cell lung cancer (NSCLC) tumors is associated with poorer outcome; however, its effect on patient outcome in advanced NSCLC has not been explored.
  
  
  METHODS
  After institutional ethical approval was obtained, demographic details, clinical variables, and outcome data were collected on consecutive NSCLC patients diagnosed at the Tom Baker Cancer Centre from 2003 to 2006 (Glans-Look Lung Cancer Database). Formalin-fixed paraffin-embedded diagnostic biopsies from stage IV patients were obtained and tissue microarrays generated. CXCR4 expression within NSCLC cells was analyzed by quantitative fluorescent immunohistochemistry using the HistoRx PM-2000 platform and then correlated with clinical outcome.
  
  
  RESULTS
  Of 832 patients, 170 had samples suitable for tissue microarray generation and analysis. Automated immunohistochemistry for CXCR4 was successfully completed on all 170 patients. High expressors had a significantly poorer median overall survival of 2.7 months versus 5.6 months for the low expressors (p = 0.0468). This difference is driven by high-expressing females who have a median overall survival of 1.6 months versus 6.4 months for the low expressors (p = 0.006).
  
  
  CONCLUSIONS
  CXCR4 is expressed in the majority of NSCLC tumors, and overexpression is associated with significantly poorer survival in stage IV NSCLC patients. Interestingly, this poor outcome is disproportionately represented in the female population. Our results suggest a gender-dependent difference in clinical outcome based on CXCR4 overexpression in stage IV NSCLC.
authors.affiliation: Translational Research Laboratory, Tom Baker Cancer Centre and University of Calgary, Calgary, Alberta, Canada.
authors.forename: Shannon
authors.initials: S
authors.lastname: Otsuka
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Klimowicz
authors.forename: Karen
authors.initials: K
authors.lastname: Kopciuk
authors.forename: Stephanie K
authors.initials: SK
authors.lastname: Petrillo
authors.forename: Mie
authors.initials: M
authors.lastname: Konno
authors.forename: Desiree
authors.initials: D
authors.lastname: Hao
authors.forename: Huong
authors.initials: H
authors.lastname: Muzik
authors.forename: Erin
authors.initials: E
authors.lastname: Stolte
authors.forename: William
authors.initials: W
authors.lastname: Boland
authors.forename: Don
authors.initials: D
authors.lastname: Morris
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Magliocco
authors.forename: D Gwyn
authors.initials: DG
authors.lastname: Bebb
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018287:Carcinoma, Large Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012189:Retrospective Studies; D012737:Sex Factors; D015996:Survival Rate; D046888:Tissue Array Analysis
chemical_list: D019718:Receptors, CXCR4