الفهرس 
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Abstract
Summary
This study aimed at evaluating the immunohistochemical expression of TIM-3 and CEACAM-1 in urothelial carcinoma in a group of Egyptian patients and studying their relations with clinical and pathological related factors.
The material of this study consisted of 60 urothelial carcinoma specimens; 37 obtained by trans-urethral resection and 23 by radical cystectomies, collected retrospectively and prospectively from the pathology lab of Beni-Suef university hospital in the form of formalin fixed paraffin embedded tissue blocks. Demographic and pathological data were obtained from patients’ reports.
The age incidence ranged from 35 to 77 years with an overall mean age 60.183 year. The male to female ratio was 3.3:1. The conventional type urothelial carcinoma was the most frequent histological differentiation. 83.3% of tumors were high grade. 64.3% of cases with submitted muscularis propria showed muscle invasion. Tumor stage T2 was the most frequent stage; 11 out of the studied 23 radical cystectomy cases and only 10 cases showed positive lymph node metastasis. Moreover, bilharzial infestation was noted in 35% of cases. The degree of associated inflammation varied and the moderate inflammation (38% of cases) was the most frequent. In addition, 26 cases showed tumor necrosis. Lymphovascular and perineural invasions were noted in 23.3% of cases.
The present study revealed that both TIM-3 and CEACAM-1 were expressed in cancer cells, tumor infiltrating lymphocytes and endothelial cells. There were significant relations between TIM-3 expression by cancer cells and tumor necrosis and TIM-3 expression by TILs. In addition, TIM-3 expression by TILs significantly related to TIM-3 expression by endothelial cells. Moreover, endothelial CEACAM-1 positivity significantly correlated to tumor grade, associated inflammation, tumor necrosis, muscle invasion and tumor differentiation. Furthermore, CEACAM-1 expression by TILs was significantly related to its expression in tumor cells and to 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 expression by TILs showed significant relation with CEACAM-1 expression by TILs.
However, no significant relations found between different TIM-3 and CEACAM-1 expressions and age, sex, tumor size, bilharziasis, perineural invasions, tumor stage and lymph node metastasis.
Regarding tumor necrosis, lymphovascular invasion and associated inflammation showed no significant correlations with different TIM-3 and CEACAM-1 expressions except for those mentioned before.
We have finally concluded that TIM-3 and CEACAM-1 may have a role in urothelial cancer development and progression and could be promising immunotherapeutic targets. Additionally, endothelial CEACAM-1 expression could be a marker of tumor progression and invasiveness.