Prognostic significance of tumour-infiltrating leukocytes in urothelial carcinoma
Karnevi E, Nodin B, Andersson G, Wennersten C, Boman K, Jirström K
Division of Oncology and Pathology,Department of Clinical Sciences, Lund University, Skåne University Hospital, 221 85 Lund, Sweden
Urothelial carcinoma (UC) is the 7th most common cancer in men and 17th in women, and about 75-80% of patients present with non-invasive disease. For the remaining 20-25%, however, muscle-invasive cancer can often prove to be fatal with limited treatment strategies. In concordance with other cancer types, UC is associated with immune cell infiltration. Among these are cytotoxic and regulatory T-cells and tumour-associated macrophages. These have previously been reported to influence clinical outcome in other tumour types but their prognostic significance in UC needs further study. Immunohistochemical staining of CD8+, Foxp3+ and CD68+ leukocytes was evaluated in tissue microarrays with tumours from 272 incident UC cases in the prospective cohort study Malmö Diet and Cancer. CD68 could be evaluated in 266 cases (97.79%) and CD8 and Foxp3 in 270 (99.26%) cases. High density of all three leukocyte subsets was found to be associated with higher T-stage and tumour grade. Furthermore, high density of Foxp3 regulatory T-cells in stroma and tumour vicinity was associated with reduced overall survival, as was high density of CD68+ macrophages in the tumour vicinity. In conclusion, this study shows a connection between high levels of tumour-infiltrating CD8+ cytotoxic T-cells, Foxp3 regulatory T-cells and CD68+ macrophages and more advanced UC tumours. In addition, high density of regulatory T-cells and macrophages was shown to be prognostic and might be of clinical relevance after further validation in additional cohorts.