Distribution of lymphocytes of the alpha(E)beta(7) phenotype and E-cadherin in normal human urothelium and bladder carcinomas.
Cresswell J., Robertson H., Neal DE., Griffiths TR., Kirby JA.
The primary aim of this work was to survey normal urothelium and transitional cell carcinoma (TCC) for the presence of T lymphocytes expressing the intraepithelial, CD103(+) phenotype. This antigen defines the alpha(E)beta(7)-integrin. The adhesive counter-receptor for alpha(E)beta(7) is E-cadherin, which is down-regulated during cancer progression. The secondary aim was to determine the pattern of distribution of CD103(+) lymphocytes in relation to E-cadherin expression in bladder cancer. Cryostat sections of normal bladder and TCC were treated with antibodies specific for human CD103, CD3, CD8 and E-cadherin. Visualization was performed by immunoperoxidase or alkaline phosphatase development with light and confocal microscopy. Dual staining and serial sections were used to assess the relationship between these antigens. Four samples of normal bladder and 26 TCC samples were assessed. Occasional T lymphocytes (CD3(+)) were seen in normal urothelium and lamina propria. In the urothelium the majority of these T lymphocytes (71%) were also CD8(+) and of these 68% expressed the CD103 marker. In the lamina propria 62% of the T lymphocytes were CD8(+) and 56% of these expressed the CD103 marker. In carcinomas significantly greater numbers of CD103(+) T lymphocytes were present in the surrounding stroma rather than infiltrating the carcinomas (P = 0.0006). Of those T lymphocytes infiltrating the tumours, 71% were CD8(+) and of these 58% expressed CD103. In the surrounding stroma 52% of lymphocytes were CD8(+) and 82% of this subset expressed CD103. Infiltration by CD103(+) lymphocytes was not related to the intensity of E-cadherin expression. T lymphocytes of the CD103(+) phenotype are present in normal urothelium where they may play a role in immunosurveillance. Rather than infiltrating into carcinomas, these cells predominate in the surrounding stroma which could suggest a failure of immune function.