title: The prognostic value of peritumoral regulatory T cells and its correlation with intratumoral cyclooxygenase-2 expression in clear cell renal cell carcinoma.
abstract: OBJECTIVE
  To investigate the prognostic value of regulatory T cells (Tregs) and its correlation with cyclooxygenase-2 (COX-2) expression in clear cell renal cell carcinoma (RCC).
  
  
  METHODS
  CD4+, Foxp3+ tumour-infiltrating lymphocytes and tumour COX-2 expression were assessed by immunohistochemistry in tissue microarrays containing RCC from 125 patients. Prognostic effects of low and high expression were evaluated by Cox regression and Kaplan-Meier analysis using the median values as thresholds. The expression of Tregs and COX-2 were compared with the clinicopathological variables. In addition, Tregs and its correlation with COX-2 expression was also analysed.
  
  
  RESULTS
  Peritumoral Tregs were positively correlated with intratumoral COX-2 expression (Spearman rank correlation 0.336, P < 0.001). Peritumoral Tregs were associated with TNM stage (P = 0.001) and tumour size (P = 0.002), while intratumoral COX-2 expression was associated with TNM stage (P = 0.018) and grade (P = 0.013). Using multivariate analysis, increased peritumoral Tregs, higher TNM stage (III + IV), larger tumour size (> or =7 cm) and higher nuclear grade (III + IV) were independent predictors for significantly shorter overall survival and disease-free survival.
  
  
  CONCLUSIONS
  Increased peritumoral Tregs are associated with worse prognosis in clear cell RCC. The high intratumoral COX-2 expression may be the underlying reason for the aberrant gathering of Tregs. These results suggest that clinical application of COX-2 inhibitors may benefit those patients with higher intratumoral COX-2 immunostaining by reducing the transformation of Tregs in RCC.
authors.affiliation: Department of Urology, Zhong Shan Hospital, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jin F
authors.initials: JF
authors.lastname: Li
authors.forename: Yi W
authors.initials: YW
authors.lastname: Chu
authors.forename: Guo M
authors.initials: GM
authors.lastname: Wang
authors.forename: Tong Y
authors.initials: TY
authors.lastname: Zhu
authors.forename: Rui M
authors.initials: RM
authors.lastname: Rong
authors.forename: Jun
authors.initials: J
authors.lastname: Hou
authors.forename: Ming
authors.initials: M
authors.lastname: Xu
mesh_terms: D000368:Aged; D015704:CD4 Antigens / Q000378:metabolism; D002292:Carcinoma, Renal Cell / Q000401:mortality / Q000473:pathology*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000401:mortality / Q000473:pathology*; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D050378:T-Lymphocytes, Regulatory / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D051546:Cyclooxygenase 2