The prognostic value of peritumoral regulatory T cells and its correlation with intratumoral cyclooxygenase-2 expression in clear cell renal cell carcinoma

BJU Int. 2009 Feb;103(3):399-405. doi: 10.1111/j.1464-410X.2008.08151.x. Epub 2008 Nov 19.

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).

Patients and 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • CD4 Antigens / metabolism
  • Carcinoma, Renal Cell / mortality
  • Carcinoma, Renal Cell / pathology*
  • Cyclooxygenase 2 / metabolism*
  • Female
  • Forkhead Transcription Factors / metabolism
  • Humans
  • Immunohistochemistry
  • Kidney Neoplasms / mortality
  • Kidney Neoplasms / pathology*
  • Lymphocytes, Tumor-Infiltrating / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Prognosis
  • Prospective Studies
  • Survival Analysis
  • T-Lymphocytes, Regulatory / metabolism*

Substances

  • CD4 Antigens
  • FOXP3 protein, human
  • Forkhead Transcription Factors
  • Cyclooxygenase 2