title: CXCR4 expression predicts patient outcome and recurrence patterns after hepatic resection for colorectal liver metastases.
abstract: BACKGROUND
  The purpose of this study was to determine if the expression of the chemokine receptors, CXCR4 and CCR7, and the chemokine ligand, CXCL12, in completely resected colorectal cancer hepatic metastases are predictive of disease-specific survival, recurrence-free survival and patterns of recurrence.
  
  
  METHODS
  Immunohistochemical analysis of CXCR4, CCR7 and CXCL12 expression within resected hepatic metastases was performed and correlated with clinicopathological variables, disease-specific survival, recurrence-free survival and patterns of recurrence.
  
  
  RESULTS
  Seventy-five patients who underwent partial hepatectomy with curative intent were studied. CXCR4 expression (hazard ratio [HR] 3.6, 95% confidence interval [95% CI] 1.4-9.1) and clinical risk score >2 (HR 2.3, 95% CI 1.1-4.7) were independently associated with disease-specific survival by multivariate analysis. The 5-year estimated disease-specific survival rates for positive and negative CXCR4 tumor expression were 44 and 77%, respectively (P = 0.005). CXCR4 expression (HR 2.2, 95% CI 1.2-4.2) and clinical risk score >2 (HR 1.9, 95% CI 1.1-3.4) were independently associated with recurrence-free survival by multivariate analysis. The five year estimated recurrence-free survival rates for positive and negative CXCR4 tumor expression were 20 and 50%, respectively (P = 0.004). Neither CXCL12 nor CCR7 expression in tumors predicted disease-specific survival or recurrence-free survival. Forty-nine patients (65%) developed recurrent disease after initial hepatectomy. Negative CXCR4 tumor expression was associated with favorable recurrence patterns amenable to salvage resection and/or ablation.
  
  
  CONCLUSIONS
  Negative CXCR4 expression in resected colorectal cancer hepatic metastases is independently associated with improved disease-specific and recurrence-free survival and favorable patterns of recurrence.
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Texas Southwestern Medical Center, Dallas, TX, USA. adam.yopp@utsouthwestern.edu
authors.forename: Adam C
authors.initials: AC
authors.lastname: Yopp
authors.forename: Jinru
authors.initials: J
authors.lastname: Shia
authors.forename: Jean M
authors.initials: JM
authors.lastname: Butte
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Allen
authors.forename: Yuman
authors.initials: Y
authors.lastname: Fong
authors.forename: William R
authors.initials: WR
authors.lastname: Jarnagin
authors.forename: Ronald P
authors.initials: RP
authors.lastname: DeMatteo
authors.forename: Michael I
authors.initials: MI
authors.lastname: D'Angelica
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000378:metabolism* / Q000556:secondary / Q000628:therapy; D054377:Chemokine CXCL12 / Q000378:metabolism; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006498:Hepatectomy; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary / Q000628:therapy; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local / Q000378:metabolism*; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D054400:Receptors, CCR7 / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000378:metabolism*; D012189:Retrospective Studies
chemical_list: C515370:CCR7 protein, human; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D054400:Receptors, CCR7; D019718:Receptors, CXCR4