title: Atypical chemokine receptors predict lymph node metastasis and prognosis in patients with cervical squamous cell cancer.
abstract: OBJECTIVE
  Atypical chemokine receptors (ACRs), including CCX-CKR, DARC, and D6, have been reported to be involved in cancer invasion and metastasis. The objective of this study was to investigate the prognostic importance of ACRs in patients with cervical squamous cell carcinoma (CSCC).
  
  
  METHODS
  The expression of three ACRs was investigated by immunohistochemical (IHC) examination in a total of 317 cervical specimens including 40 normal cervical tissues, 50 cases of carcinoma in situ of cervix (CIS), and 227 cases of CSCC by immunohistochemistry.
  
  
  RESULTS
  The expression rate of DARC and CCX-CKR in CSCC, CIS, and normal cervix increased gradually (p<0.01). D6 expression is decreased in CSCC compared to either in CIS or in normal cervix (p<0.05). In addition, the expression of CCL2 and CCL19 was inversely associated with ACR expression (p<0.05), while that of LCA was positively correlated with ACR expression (p<0.05). Moreover, DARC expression, CCX-CKR expression, and ACR coexpression were negatively correlated with lymph node metastasis (P<0.01). D6 expression and ACR coexpression were negatively related to tumor size (p=0.018) and recurrence (p=0.028). In multivariate Cox regression analysis, CCX-CKR expression was a positive indicator for overall survival (p=0.008), and D6 expression was an independent predictor of both overall and recurrence-free survival (p=0.041) in CSCC.
  
  
  CONCLUSIONS
  Our results suggest that the loss of ACRs may play important roles in the tumorigenesis and migration of cervical cancer. ACR expression may be considered as prognostic markers in patients with CSCC.
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, GD 510060, China.
authors.forename: Teng
authors.initials: T
authors.lastname: Hou
authors.forename: Dongxia
authors.initials: D
authors.lastname: Liang
authors.forename: Liqun
authors.initials: L
authors.lastname: Xu
authors.forename: Xin
authors.initials: X
authors.lastname: Huang
authors.forename: Yongwen
authors.initials: Y
authors.lastname: Huang
authors.forename: Yanna
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology*; D054415:Chemokine CCL19 / Q000378:metabolism; D018932:Chemokine CCL2 / Q000378:metabolism; D018572:Disease-Free Survival; D004375:Duffy Blood-Group System / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D015999:Multivariate Analysis; D016612:Paraffin Embedding; D011379:Prognosis; D016016:Proportional Hazards Models; D054388:Receptors, CCR / Q000378:metabolism; D054447:Receptors, CCR10 / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D019707:Receptors, Chemokine / Q000378:metabolism*; D012044:Regression Analysis; D002583:Uterine Cervical Neoplasms / Q000378:metabolism* / Q000473:pathology*; D000097628:Chemokine Receptor D6
chemical_list: D054415:Chemokine CCL19; D018932:Chemokine CCL2; D004375:Duffy Blood-Group System; D054388:Receptors, CCR; D054447:Receptors, CCR10; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D000097628:Chemokine Receptor D6; C473745:ACKR1 protein, human; C408223:ACKR4 protein, human; C515460:CCL19 protein, human; C111835:CCL2 protein, human