Abstract

Background: In Egypt, Urinary bladder carcinoma is a common malignancy accounting for 14.3% of total malignancies in both sexes with a 3:1 M: F ratio. To reduce bladder cancer morbidity and mortality, identification of tumor markers specific enough for prognosis and can serve as an effective anti-cancer target is urgent. The purpose of this study is to evaluate the role of Trop2, Cyclin D1, FOXP3 and their relationship with the established clinicopathological parameters and overall survival of bladder cancer patients. Methods: Using the standard immunohistochemical technique in 80 primary bladder carcinomas and 20 specimens as non-neoplastic groups. The malignant group included 50 cases of muscle-invasive and 30 cases of non-muscle invasive bladder cancer. Results: significant association of overexpressed Trop2 and FOXP3 with high grade, advanced stage, lymph node involvement, and high mitotic count. On the other hand, Cyclin D1 displayed a favorable prognostic impact and an inverse relation with Trop2 and FOXP3. A direct correlation between both FOXP3 expression in malignant cells and peritumoral TIL FOXP3+ expression was displayed. Trop2, Cyclin D1, FOXP3 expression didn’t affect the overall survival of the studied sample. Conclusions: The inverse relation between Cyclin D1 and Trop2 proposes the consumption of Cyclin D1 by Trop2 as a ligand in the urinary bladder carcinogenesis. A synergistic role and a cross-talk between TIL FOXP3+ and tumoral FOXP3 + cells are anticipated. Trop2 and FOXP3 could be a promising potential biomarkers for identifying patients with poor prognostic factors in bladder cancer serving as potential targets for cancer therapy

Highlights

  • In Egypt, Urinary bladder carcinoma is a common malignancy accounting for 14.3% of total malignancies in both sexes with a 3:1 M: F ratio

  • Membranous Trop2 was exclusively associated with the malignant group (p=0.005) while patchy cytoplasmic FOXP3 was in favor of non-neoplastic group (p=0.011 and 0.001)

  • Regarding the peritumoral FOXP3 expression, positive FOXP3 was statistically in favor of inflammatory stromal reaction (P=0.001) and advanced stage, for 21 out of 33 Tumor infiltrating lymphocytes (TILs) FOXP3 positive cases were observed in the advanced stage bladder cancer (P=0.001) (Table 6)

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Summary

Introduction

In Egypt, Urinary bladder carcinoma is a common malignancy accounting for 14.3% of total malignancies in both sexes with a 3:1 M: F ratio. The purpose of this study is to evaluate the role of Trop, Cyclin D1, FOXP3 and their relationship with the established clinicopathological parameters and overall survival of bladder cancer patients. The malignant group included 50 cases of muscle-invasive and 30 cases of non-muscle invasive bladder cancer. Cyclin D1 displayed a favorable prognostic impact and an inverse relation with Trop and FOXP3. A direct correlation between both FOXP3 expression in malignant cells and peritumoral TIL FOXP3+ expression was displayed. Cyclin D1, FOXP3 expression didn’t affect the overall survival of the studied sample. Trop and FOXP3 could be a promising potential biomarkers for identifying patients with poor prognostic factors in bladder cancer serving as potential targets for cancer therapy

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