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

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 immu...

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Main Authors: Abla Sayed Mahmoud, Sahar Ali Daoud, Wesam Ismail Moustafa, Osama Sayed, Badawia Bayoumi Ibrahim, Marwa Mohamed Sayed, Sarah Abdelrahman Mohammed
Format: Article
Language:English
Published: Beni-Suef University, Faculty of Medicine 2021-06-01
Series:Egyptian Journal of Medical Research
Subjects:
Online Access:https://ejmr.journals.ekb.eg/article_175726_6a07f93b46e4caf89c3e19ef3c4ee602.pdf
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author Abla Sayed Mahmoud
Sahar Ali Daoud
Wesam Ismail Moustafa
Osama Sayed
Badawia Bayoumi Ibrahim
Marwa Mohamed Sayed
Sarah Abdelrahman Mohammed
author_facet Abla Sayed Mahmoud
Sahar Ali Daoud
Wesam Ismail Moustafa
Osama Sayed
Badawia Bayoumi Ibrahim
Marwa Mohamed Sayed
Sarah Abdelrahman Mohammed
author_sort Abla Sayed Mahmoud
collection DOAJ
description 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.
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spelling doaj.art-a8b8aee4582444bca3fa2359a40953572023-02-27T17:41:46ZengBeni-Suef University, Faculty of MedicineEgyptian Journal of Medical Research2682-43962682-440X2021-06-012222724910.21608/ejmr.2021.175726175726Expression Of TIM-3 And CEACAM-1 In Bladder Urothelial Carcinoma ( Immunohistochmical And Histopathological Study )Abla Sayed Mahmoud0Sahar Ali Daoud1Wesam Ismail Moustafa2Osama Sayed3Badawia Bayoumi Ibrahim4Marwa Mohamed Sayed5Sarah Abdelrahman Mohammed6Pathology department, Faculty of medicine, Beni- Suef University, Beni- Suef, EgyptPathology department, Faculty of medicine, Beni- Suef University, Beni- Suef, EgyptPathology department, Faculty of medicine, Beni- Suef University, Beni- Suef, EgyptUrology department, Faculty of medicine, Beni- Suef University, Beni-Suef, EgyptPathology department, Faculty of medicine, Cairo University, Cairo, EgyptPathology department, Faculty of medicine, Beni- Suef University, Beni- Suef, EgyptPathology department, Faculty of medicine, Beni- Suef University, Beni- Suef, EgyptBackground 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.https://ejmr.journals.ekb.eg/article_175726_6a07f93b46e4caf89c3e19ef3c4ee602.pdftim-3ceacam-1urothelial carcinomaimmunotherapy
spellingShingle Abla Sayed Mahmoud
Sahar Ali Daoud
Wesam Ismail Moustafa
Osama Sayed
Badawia Bayoumi Ibrahim
Marwa Mohamed Sayed
Sarah Abdelrahman Mohammed
Expression Of TIM-3 And CEACAM-1 In Bladder Urothelial Carcinoma ( Immunohistochmical And Histopathological Study )
Egyptian Journal of Medical Research
tim-3
ceacam-1
urothelial carcinoma
immunotherapy
title Expression Of TIM-3 And CEACAM-1 In Bladder Urothelial Carcinoma ( Immunohistochmical And Histopathological Study )
title_full Expression Of TIM-3 And CEACAM-1 In Bladder Urothelial Carcinoma ( Immunohistochmical And Histopathological Study )
title_fullStr Expression Of TIM-3 And CEACAM-1 In Bladder Urothelial Carcinoma ( Immunohistochmical And Histopathological Study )
title_full_unstemmed Expression Of TIM-3 And CEACAM-1 In Bladder Urothelial Carcinoma ( Immunohistochmical And Histopathological Study )
title_short Expression Of TIM-3 And CEACAM-1 In Bladder Urothelial Carcinoma ( Immunohistochmical And Histopathological Study )
title_sort expression of tim 3 and ceacam 1 in bladder urothelial carcinoma immunohistochmical and histopathological study
topic tim-3
ceacam-1
urothelial carcinoma
immunotherapy
url https://ejmr.journals.ekb.eg/article_175726_6a07f93b46e4caf89c3e19ef3c4ee602.pdf
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