Expression Of TIM-3 And CEACAM-1 In Bladder Urothelial Carcinoma ( Immunohistochmical And Histopathological Study )

Abstract

Background and objectives: Urothelial carcinoma is now considered to be the most important tumor of the urinary bladder in Egypt especially after decreased prevalence of schistosomiasis. Due to few available therapeutic approaches and partial success in improving patients' survival, novel immunotherapeutic agents such as immune checkpoint inhibitors become a promising hope especially after PD-1 and CTLA-4 being clinically relevant. TIM-3 which is another immune checkpoints molecule is recently appeared to be associated with immune suppression in many tumors and has been reported to be aberrantly expressed in several human malignancies including urothelial carcinoma. One of the TIM-3 discovered ligands is CEACAM-1. The latter has been linked to malignancy progression and metastatic spread and has been expressed in many tumor types. The aim of our work is to evaluate the expression of TIM-3 and CEACAM-1 in bladder urothelial carcinoma and analyse their correlations with clinical and pathological related factors. Methods: Different TIM-3 and CEACACM-1 expressions were evaluated in immunohistochemically stained paraffin embedded sections from 60 Egyptian patients with bladder urothelial carcinoma. Expression was correlated with the available clinical and pathological data. Results: Both TIM-3 and CEACAM-1 were expressed in cancer cells, tumor infiltrating lymphocytes and endothelial cells. TIM-3 expression by cancer cells showed significant correlation with tumor necrosis and TIM-3 expression by TILs. TIM-3 expression by TILs significantly related to TIM-3 expression by endothelial cells. Endothelial CEACAM-1 positivity significantly correlated to tumor grade, associated inflammation, tumor necrosis, muscle invasion and tumor differentiation. CEACAM-1 expression by TILs was significantly related to its expression in tumor cells and absent vascular emboli. Regarding correlations between the both studied markers, expression of TIM-3 by cancer cells was significantly correlated to CEACAM-1 expression by both TILs and endothelial cells. In addition, TIM-3 and CEACAM-1 expressions by TILs were significantly positively correlated. Conclusion: The expressions of TIM-3 and CEACAM-1 in urothelial cancer cells and TILs suggest a potential role for these molecules in cancer development and progression and introduce them as a novel targets in bladder cancer therapy. In addition, endothelial CEACAM-1 expression could be a marker of tumor progression and invasiveness.

Keywords

• tim-3
• ceacam-1
• urothelial carcinoma
• immunotherapy