FOXP3 and survival in urinary bladder cancer

Abstract

What's known on the subject? and What does the study add? This is the first study examining FOXP3 expression in invasive urothelial urinary bladder cancer and in their tumour-infiltrating lymphocytes (TILs). The relation of their respective immunohistological expression to survival adds new knowledge in the fields of tumour immunology and prognostic markers. OBJECTIVE • To investigate the possible impact of FOXP3 expression in T-cells, as well as in tumour cells, on long-term survival in patients with urinary bladder cancer (UBC) invading muscle. PATIENTS AND METHODS • In a retrospective study, tumour specimens from 37 patients cystectomized for T1–T4 UBC during 1999–2002 at the Karolinska University Hospital were examined by immunohistochemistry for tumour expression and/or infiltration of immune cells expressing FOXP3 as well as CD3. • The results obtained were correlated with clinicopathological parameters, where the primary and secondary outcomes investigated were overall survival and progression-free survival, respectively. RESULTS • Infiltration of CD3⁺ and FOXP3⁺ lymphocytes (≥3 cells per high-power field) were both correlated with better survival, and this relationship persisted throughout the whole study period (all P < 0.05). • Patients with FOXP3⁺ tumour cells had decreased long-term survival compared to those patients with FOXP3⁻ tumours (P < 0.05). • Despite a limited amount of patient material, the results of the present study indicate that FOXP3 expression, in both lymphocytes and tumour cells, is an important prognostic factor in UBC. CONCLUSIONS • FOXP3 expression in UBC cells is associated with decreased long-term survival and thus may be a novel negative prognostic factor in UBC invading muscle. • By contrast, the presence of FOXP3⁺ tumour-infiltrating lymphocytes was correlated with a positive prognosis. Because FOXP3 is up-regulated upon activation in human T-cells, FOXP3 may serve more as an activation marker than as a regulatory T-cell indicator in this case. • These results support the need for larger prospective studies aiming to confirm the results obtained and to examine the underlying mechanisms in detail.