Significance of Vascular Endothelial Growth Factor Expression in the Bladder Urothelial Carcinoma and Its Association with Tumor Grade and Invasiveness

Abstract

Scan to discover onlineBackground & Objective: Vascular Endothelial Growth Factor (VEGF) is one of the newer molecular markers that acts as a central mediator of tumor angiogenesis and is essential for tumor growth, progression, and metastasis. So anti-angiogenic drugs can be used as anticancer therapy. Treatments with anti-VEGF (Bevacizumab) therapy have been proved to improve relapse-free survival in many tumors. Urinary bladder tumor has become emerging cancer globally among elderly individuals. So, the identification and development of novel biomarkers for effective treatment of urinary bladder carcinoma is essential. The present study aimed to investigate the immunohistochemical expression of VEGF in urothelial carcinoma of urinary bladder and to assess its association with tumor grade and muscle invasiveness. Methods:This cross-sectional study was conducted in the Department of Pathology, Chittagong Medical College, Chattogram from September 2018 to August 2020. Fifty-six formalin-fixed paraffin-embedded tissue blocks of urinary bladder carcinoma were prepared for both histopathological and immunohistochemical examination. Each slide was evaluated by at least two pathologists.Results: Weak to strong positive expression of VEGF were observed in 52 cases (92.86%). The proportion of tumors positive for VEGF expression was higher among patients with high grade and non-muscle invasive bladder carcinoma. Conclusion:We found that VEGF expression has a significant association with tumor grade and an inverse association with muscle invasion. These findings may be useful for selecting the subset of patients likely to respond to anti-VEGF targeted therapy.

Diagnostic and Therapeutic Implications of Sortilin Expressed on the Surface of Bladder Carcinoma Cells

“…Such significant variation in cell surface expression of sortilin between normal and cancer cells makes sortilin an ideal target for cancer diagnosis and therapy. Significant expression of VEGF has been reported to be associated with low-grade bladder carcinoma (9), which would be a good candidate to be used along with sortilin as a prognostic and therapeutic marker. So, concurrent use of anti-sortilin and anti-VEGF antibodies for targeted immunotherapy of bladder carcinoma is suggested.…”

“…Among cancer therapy strategies, the passive immune-therapies by monoclonal antibodies targeting cell surface antigens gained attention to combat different types of malignancies (5)(6)(7). Numerous studies have demon-strated therapeutic and prognostic values of biomarkers in urothelial carcinoma and other urinary tract tumors, like PMSA in prostate cancer (8) CXR2 and CXR3 in renal cell carcinoma (9) and CD38 and Zap-70 in CLL (10). Consequently, sortilin and its functional role in bladder cancer might be considered as a novel diagnostic and therapeutic agent in bladder carcinoma.…”

Influence of the grade and invasiveness of bladder cancer on disease course severity in patients with bladder tamponade resulting from a bleeding bladder cancer

“…found that VEGF expression shows a significant association with bladder cancer grade. [ 11 ] A number of other authors reported that higher microvessel density is significantly associated with the advanced T stage and high histological grade of bladder tumors. [ 12 - 14 ] Increased vascularization of higher-grade and more invasive tumors could potentially lead to more profuse bleeding, more severe anemia, and a greater need for transfusions, and consequently to a more severe disease course and a longer hospitalization.…”

A Short Overview on Therapeutic Biomarkers for Muscle Invasive Bladder Carcinoma

“…37,38 Again, some studies showed that VEGF expression was significantly higher in non-MIBC compared to MIBC as the rate of tumour growth is higher at the early stage of the disease. 39,40 So, the inhibition of VEGF transcripts significantly reduces the proliferation rate of the bladder cancer cells 41 and blockade of VEGF receptor reduces growth and invasion of bladder cancer cells. 42,43 Bevacizumab (VEGF antibody) and ramucirumab (VEGFR2 antibody), used in combination with chemotherapy, showed promising result in Phase II clinical studies of advanced UC.…”