Thrombomodulin Expression in Bladder Cancer Tissue and Its Association with Prognosis and Patient Survival

Joanne Watt, Daniel G Maguire, Cherith N Reid, John V Lamont, Stephen P Fitzgerald, Mark W Ruddock Randox Laboratories Ltd, Molecular Biology, Crumlin, County Antrim BT29 4QY, Northern Ireland, UKCorrespondence: Mark W RuddockRandox Laboratories Ltd, Molecular Biology, 55 Diamond Road, Crumlin, County Antrim BT29 4QY, Northern Ireland, United KingdomTel +44 28 9442 2413Fax +44 28 9445 2912Email Mark.Ruddock@randox.comBackground: Decreased expression of thrombomodulin (TM) in bladder cancer tissue has been shown to be associated with cell proliferation, increased malignancy and a poor prognosis. The aim of this study was to investigate the immunoexpression of TM in bladder tissue cores by immunohistochemistry (IHC) and the relationship between TM score and patient survival for the following pathologies: transitional cell papillary carcinoma (TCPC), transitional cell carcinoma (non-papillary) (TCC), squamous cell carcinoma (SCC), adenocarcinoma, and sarcoma. TM immunoexpression was also evaluated in normal adjacent bladder tissue cores.Methods: TM immunoexpression was assessed in n=185 formalin-fixed paraffin-embedded (FFPE) bladder tissue cores from n=98 patients by IHC. Tissue cores included TCPC (n=29), TCC (n=85), SCC (n=21), adenocarcinoma (n=12), sarcoma (n=4), and normal tissue cores (n=34).Results: TM immunoexpression scores are stronger in TCPC, TCC and SCC bladder cancer tissue cores with respect to adenocarcinoma and sarcoma (mean TM immunoexpression scores: 3.04, 2.57, 2.55, 1.55 and 1.19, respectively) (Kruskal–Wallis p< 0.001). TM immunoexpression scores significantly decreased in bladder cancer tissue cores across both stage (p< 0.001) and grade (p< 0.001) (Kruskal–Wallis). Survival data were available for n=45 bladder cancer patients (mean follow-up of 34 months). Applying a TM immunoexpression cut-off score of 3.0 demonstrated that patients with bladder cancer who had a TM immunoexpression score < 3.0 had lower survival rates (median survival 23.5 months). In contrast, patients with TM immunoexpression scores ≥ 3.0 had longer survival rates (median survival 40 months) (log-rank; p=0.045).Conclusion: TM immunoexpression in bladder cancer tissue may be a clinically relevant predictor of tumor progression and survival. Low expression of TM in bladder cancer biopsies or in recurrent bladder cancer may be indicative of a poor prognosis. TM immunoexpression could be used to guide clinical decision making.Keywords: transitional urothelial carcinoma, tissue microarrays, immunohistochemistry, bladder cancer