Expression patterns of the immune checkpoint ligand CD276 in urothelial carcinoma

Background: CD276 is an immune checkpoint molecule. Elevated CD276 expression by urothelial carcinoma is associated with poor prognosis, but little is known about its expression across different tumor stages. We therefore investigated CD276 expression in bladder cancer (BC) cells and in tissue samples of BC stages from pT2 to pT4. Methods: CD276 expression was explored in 4 urothelial cancer cell lines and 4 primary normal urothelial cell populations by quantitative RT-PCR, Western blot and flow cytometry. CD276 was investigated in bladder tumors from 98 patients by immunohistochemistry using a score (0–300) incorporating both, staining intensity and area of CD276 staining. Normal appearing urothelium in the bladder of the same patients served as controls. Results: The urothelial carcinoma cell lines expressed significantly higher levels of CD276 on transcript (p < 0.006), total protein levels (p < 0.005), and on the cell surface (p < 0.02) when compared to normal urothelial cells. In pT2–T4 tumor tissue samples, CD276 was overexpressed (median score 185) when compared to corresponding healthy tissues from the same patients (median score 50; p < 0.001). No significant differences in CD276 expression were recorded in late, locally advanced ≥ pT3a tumors (median score 185) versus organ-confined < pT3a tumors (median score 190), but it was significantly lower in the normal urothelial tissue associated with ≥ pT3a tumors (median score 40) versus < pT3a tumors (median score 80; p < 0.05). Conclusion: CD276 expression is significantly elevated in urothelial carcinoma cells in all stages but varies between individuals considerably. Reduced CD276 expression in normal urothelial cells may imply that these cells would be protected from CD276-mediated immuno therapies.Other UBCNon UBCReviewedFacult

Microhematuria assessment an IBCN consensus-Based upon a critical review of current guidelines

RATIONALE: Assessment of patients with asymptomatic microhematuria (aMh) has been a challenge to urologists for decades. The aMh is a condition with a high prevalence in the general population and also an established diagnostic indicator of bladder cancer. Acknowledging aMh needs to be assessed within a complex context, multiple guidelines have been developed to identify individuals at high risk of being diagnosed with bladder cancer. MATERIAL & METHODS: This structured review and consensus of the International Bladder Cancer Network (IBCN) identified and examined 9 major guidelines. These recommendations are partly based on findings from a long-term study on the effects of home dipstick testing, but also on the assumption that early detection of malignancy might be beneficial. RESULTS: Despite similar designs, these guidelines differ in a variety of parameters including definition of aMh, rating of risks, use of imaging modalities, and the role of urine cytology. In addition, recommendations for further follow-up after negative initial assessment are controversial. In this review, different aspects for aMh assessment are analyzed based upon the evidence currently available. DISCUSSION: We question whether adherence to the complicated algorithms as recommended by most guidelines is practical for routine use. Based upon a consensus, the authors postulate a need for better tools. New concepts for risk assessment permitting improved risk stratification and prepone cystoscopy before refined imaging procedures (computed tomography scan and magnetic resonance imaging) are suggested

Identification of the best complete blood count-based predictors for bladder cancer outcomes in patients undergoing radical cystectomy

BACKGROUND: We sought to determine which parsimonious combination of complete blood count (CBC)-based biomarkers most efficiently predicts oncologic outcomes in patients undergoing radical cystectomy (RC) for bladder cancer (BC). METHODS: Using our institutional RC database (1992-2012), nine CBC-based markers (including both absolute cell counts and ratios) were evaluated based on pre-treatment measurements. The outcome measures were recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). Time-dependent receiver-operating characteristics curves were used to characterise each biomarker. The CBC-based biomarkers, along with several clinical predictors, were then considered for inclusion in predictive multivariable Cox models based on the Akaike Information Criterion. RESULTS: Our cohort included 418 patients. Neutrophil-lymphocyte ratio (NLR) was the only biomarker satisfying criteria for inclusion into all models, independently predicting RFS (HR per 1-log unit=1.52, 95% CI=1.17-1.98, P=0.002), CSS (HR=1.47, 95% CI=1.20-1.80, P<0.001), and OS (HR=1.56, 95% CI=1.16-2.10, P=0.004). Haemoglobin was also independently predictive of CSS (HR per 1 g/dl=0.91, 95% CI=0.86-0.95, P<0.001) and OS (HR=0.90, 95% CI=0.88-0.93, P<0.001), but not RFS. CONCLUSIONS: Among CBC biomarkers studied, NLR was the most efficient marker for predicting RFS, whereas NLR and haemoglobin were most efficient in predicting CSS and OS. NLR and haemoglobin are promising, cost-effective, independent biomarkers for predicting oncologic BC outcomes following RC. CONDENSED ABSTRACT: Various CBC-based biomarkers have separately been shown to be predictive of oncologic outcomes in patients undergoing cystectomy for BC. Our study evaluated these biomarkers, and determined that NLR is the best CBC-based biomarker for predicting RFS, whereas NLR and haemoglobin are most efficient for predicting CSS and OS