Performance of Survivin mRNA as a Biomarker for Bladder Cancer in the Prospective Study UroScreen

BACKGROUND: Urinary biomarkers have the potential to improve the early detection of bladder cancer. Most of the various known markers, however, have only been evaluated in studies with cross-sectional design. For proper validation a longitudinal design would be preferable. We used the prospective study UroScreen to evaluate survivin, a potential biomarker that has multiple functions in carcinogenesis. METHODS/RESULTS: Survivin was analyzed in 5,716 urine samples from 1,540 chemical workers previously exposed to aromatic amines. The workers participated in a surveillance program with yearly examinations between 2003 and 2010. RNA was extracted from urinary cells and survivin was determined by Real-Time PCR. During the study, 19 bladder tumors were detected. Multivariate generalized estimation equation (GEE) models showed that β-actin, representing RNA yield and quality, had the strongest influence on survivin positivity. Inflammation, hematuria and smoking did not confound the results. Survivin had a sensitivity of 21.1% for all and 36.4% for high-grade tumors. Specificity was 97.5%, the positive predictive value (PPV) 9.5%, and the negative predictive value (NPV) 99.0%. CONCLUSIONS: In this prospective and so far largest study on survivin, the marker showed a good NPV and specificity but a low PPV and sensitivity. This was partly due to the low number of cases, which limits the validity of the results. Compliance, urine quality, problems with the assay, and mRNA stability influenced the performance of survivin. However, most issues could be addressed with a more reliable assay in the future. One important finding is that survivin was not influenced by confounders like inflammation and exhibited a relatively low number of false-positives. Therefore, despite the low sensitivity, survivin may still be considered as a component of a multimarker panel

ARTEFACTS: How do we want to deal with the future of our one and only planet?

The European Commission’s Science and Knowledge Service, the Joint Research Centre (JRC), decided to try working hand-in-hand with leading European science centres and museums. Behind this decision was the idea that the JRC could better support EU Institutions in engaging with the European public. The fact that European Union policies are firmly based on scientific evidence is a strong message which the JRC is uniquely able to illustrate. Such a collaboration would not only provide a platform to explain the benefits of EU policies to our daily lives but also provide an opportunity for European citizens to engage by taking a more active part in the EU policy making process for the future. A PILOT PROGRAMME To test the idea, the JRC launched an experimental programme to work with science museums: a perfect partner for three compelling reasons. Firstly, they attract a large and growing number of visitors. Leading science museums in Europe have typically 500 000 visitors per year. Furthermore, they are based in large European cities and attract local visitors as well as tourists from across Europe and beyond. The second reason for working with museums is that they have mastered the art of how to communicate key elements of sophisticated arguments across to the public and making complex topics of public interest readily accessible. That is a high-value added skill and a crucial part of the valorisation of public-funded research, never to be underestimated. Finally museums are, at present, undergoing something of a renaissance. Museums today are vibrant environments offering new techniques and technologies to both inform and entertain, and attract visitors of all demographics.JRC.H.2-Knowledge Management Methodologies, Communities and Disseminatio

Chromosomal instability and bladder cancer: the UroVysionTM test in the UroScreen study

What’s known on the subject? and What does the study add? UroVysion™ is a multicolour fluorescence in situ hybridisation assay that detects DNA gain at chromosomes 3, 7 and 17 and loss at the 9p21 locus in exfoliated urothelial cells. This cell-based test is time-consuming and costly compared with voided urine cytology or other molecular markers for the early detection of bladder cancer. We determined copy number changes at chromosomes 3, 7 and 17 and at the 9p21 locus with UroVysion in a prospective screening study among chemical workers. Strong correlations between DNA gains yield a similar performance in detecting bladder cancer with just one of the probes for chromosomes 3, 7 or 17 instead of all, supporting the development of a simpler and cheaper assay

Selected sample characteristics of false-negative cases.

1<p>For cases 1 and 12 no samples were available for survivin determination.</p>2<p>Negative at last (0 months), positive at previous screen (14 months).</p

Potential predictors of a positive survivin test result based on GEE models that included only urine samples with complete information on all variables (190 positive survivin tests in 4546 samples from 1273 participants of UroScreen).

<p>This analysis was performed with samples of subcohort A only because not all parameters were available for the full data set. N_pos: number of samples positive for survivin, OR: odds ratio, CI: confidence interval.</p>*<p>Bladder cancer detected during UroScreen.</p>**<p>After standardization.</p

Characteristics and test results of cases.

<p>Results are from the last screening round before diagnosis.</p>1<p>Cases number 1 and 12 are omitted because no samples were available for survivin determination.</p>2<p>Traces = 1–5 leukocytes, medium = 5–<250 leukocytes, abundant ≥250 leukocytes (dipstick or microscopic sediment analysis).</p>3<p>cut-off: 10,000 (Qiagen/FDI), 40,000 (Invitek/FDI), 100,000 (Invitek/IPA).</p

Characteristics of male participants of UroScreen with former occupational exposure to aromatic amines.

*<p>One person with two tumors.</p

Cancer predictive values of the last survivin test before diagnosis of bladder cancer.

<p>Cancer predictive values of the last survivin test before diagnosis of bladder cancer.</p