Abstract
BackgroundBladder cancer (BC) is the 10th most common cancer in the UK, with about 10,000 new cases annually. About 75–85% of BC are non-muscle invasive (NMIBC), which is associated with high recurrence and progression rates (50–60% within 7–10 years). There are no routine biomarkers currently available for identifying BC patients at increased risk of developing recurrence. The focus of this research study was to evaluate antibody expression in BC patients and their association with cancer recurrence.Methods35 patients scheduled for TURBT were recruited after written informed consent. Ethical approval for the project was granted via IRAS (REC4: 14/WA/0033). Following surgical procedure, tissues were preserved in 10% buffered formalin and processed within 24 h in FFPE blocks. 7 sections (4 µm each) were cut from each block and stained for CD31, Human epidermal growth factor receptor-2 (HER-2), S100P, Cyclooxygenase-2 (COX-2), VEGFR-3 thrombomodulin and CEACAM-1 using immunohistochemistry. Clinical outcome measures (obtained via cystoscopy) were monitored for up to 6 months following surgical procedure.ResultsThere was significantly increased expression of CD31 (p < 0.001), HER-2 (p = 0.032), S100P (p < 0.001), COX-2 (p < 0.001), VEGFR-3 (p < 0.001) and decreased expression of thrombomodulin (p = 0.010) and CEACAM-1 (p < 0.001) in bladder tumours compared to normal bladder tissues. HER-2 expression was also significantly associated with cancer grade (p = 0.003), especially between grade 1 and grade 2 (p = 0.002) and between grade 1 and grade 3 (p = 0.004). There was also a significant association between cancer stage and HER-2 expression (p < 0.001). Although recurrence was significantly associated with cancer grade, there was no association with antibody expression.ConclusionFindings from the present study may indicate an alternative approach in the monitoring and management of patients with BC. It is proposed that by allowing urological surgeons access to laboratory markers such as HER-2, Thrombomodulin and CD31 (biomarker profile), potentially, in the future, these biomarkers may be used in addition to, or in combination with, currently used scoring systems to predict cancer recurrence. However, verification and validation of these biomarkers are needed using larger cohorts.
Highlights
Bladder cancer (BC) is the 10th most common cancer in the UK, with about 10,000 new cases annu‐ ally
It is proposed that by allowing urological surgeons access to laboratory markers such as Human epidermal growth factor receptor-2 (HER-2), Thrombomodulin and CD31, potentially, in the future, these biomarkers may be used in addition to, or in combination with, currently used scoring systems to predict cancer recurrence
Subjects recruited for this research attended the Betsi Cadwaladr University Health Board (BCUHB) Wrexham Maelor Hospital, North Wales for elective procedures for the treatment/management of BC (Table 1). 35 patients prospective patients scheduled for a Transurethral Resection of the Bladder tumour (TURBT) for the treatment of BC, Table 1 Demographic and clinical characteristics of recruited subjects
Summary
Bladder cancer (BC) is the 10th most common cancer in the UK, with about 10,000 new cases annu‐ ally. About 75–85% of BC are non-muscle invasive (NMIBC), which is associated with high recurrence and progression rates (50–60% within 7–10 years). There are no routine biomarkers currently available for identifying BC patients at increased risk of developing recurrence. The focus of this research study was to evaluate antibody expression in BC patients and their association with cancer recurrence. There were approximately 549,393 new bladder cancer (BC) diagnoses in 2018 of which about 90% are Transitional cell carcinomas (TCC) [1]. High recurrence rates in NMIBC means patients are exposed to frequent hospital visits with increased risks of infection and post-operative complications. Insufficient resection has been associated with an increased risk of early recurrence [2]. There is intense ongoing BC-related research, no routinely used biomarkers exist for predicting recurrence following TURBT. Cyclooxygenase-2 (COX-2) plays important roles in the inflammatory response [3] with high expression of COX-2 being reported in high grade and high stage colorectal cancer [4] and endometrial carcinoma [5]
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