title: Prognostic value of the expression of C-Chemokine Receptor 6 and 7 and their ligands in non-metastatic breast cancer.
abstract: BACKGROUND
  Chemokines and chemokine receptors are major actors of leukocytes trafficking and some have been shown to play an important role in cancer metastasis. Chemokines CCL19, CCL20 and CCL21 and their receptors CCR6 and CCR7, were assessed as potential biomarkers of metastatic dissemination in primary breast cancer.
  
  
  METHODS
  Biomarker expression levels were evaluated using immunohistochemistry on paraffin-embedded tissue sections of breast cancer (n = 207).
  
  
  RESULTS
  CCR6 was expressed by tumor cells in 35% of cases. CCR7 was expressed by spindle shaped stromal cells in 43% of cases but not by tumor cells in this series. CCL19 was the only chemokine found expressed in a significant number of breast cancers and was expressed by both tumor cells and dendritic cells (DC). CCR6, CCL19 and CCR7 expression correlated with histologic features of aggressive disease. CCR6 expression was associated with shorter relapse-free survival (RFS) in univariate and but not in multivariate analysis (p = 0.0316 and 0.055 respectively), and was not associated with shorter overall survival (OS). Expression of CCR7 was not significantly associated with shorter RFS or OS. The presence of CCL19-expressing DC was associated with shorter RFS in univariate and multivariate analysis (p = 0.042 and 0.020 respectively) but not with shorter OS.
  
  
  CONCLUSIONS
  These results suggest a contribution of CCR6 expression on tumor cells and CCL19-expressing DC in breast cancer dissemination. In our series, unlike what was previously published, CCR7 was exclusively expressed on stromal cells and was not associated with survival.
authors.affiliation: Department of Medecine, Centre Léon Bérard, Lyon, France. cassierp@hotmail.com
authors.forename: Philippe A
authors.initials: PA
authors.lastname: Cassier
authors.forename: Isabelle
authors.initials: I
authors.lastname: Treilleux
authors.forename: Thomas
authors.initials: T
authors.lastname: Bachelot
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ray-Coquard
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bendriss-Vermare
authors.forename: Christine
authors.initials: C
authors.lastname: Ménétrier-Caux
authors.forename: Olivier
authors.initials: O
authors.lastname: Trédan
authors.forename: Sophie
authors.initials: S
authors.lastname: Goddard-Léon
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Pin
authors.forename: Hervé
authors.initials: H
authors.lastname: Mignotte
authors.forename: Clarisse
authors.initials: C
authors.lastname: Bathélémy-Dubois
authors.forename: Christophe
authors.initials: C
authors.lastname: Caux
authors.forename: Serge
authors.initials: S
authors.lastname: Lebecque
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Blay
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000401:mortality / Q000503:physiopathology*; D019744:Chemokines, C / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008024:Ligands; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D054399:Receptors, CCR6 / Q000378:metabolism*; D054400:Receptors, CCR7 / Q000378:metabolism*; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis
chemical_list: D019744:Chemokines, C; D008024:Ligands; D054399:Receptors, CCR6; D054400:Receptors, CCR7