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Urinary Bladder Neoplasms: HELP
Articles by Glen Kristiansen
Based on 13 articles published since 2009
(Why 13 articles?)

Between 2009 and 2019, Glen Kristiansen wrote the following 13 articles about Urinary Bladder Neoplasms.
+ Citations + Abstracts
1 Guideline Update for the practicing pathologist: The International Consultation On Urologic Disease-European association of urology consultation on bladder cancer. 2015

Amin, Mahul B / Smith, Steven C / Reuter, Victor E / Epstein, Jonathan I / Grignon, David J / Hansel, Donna E / Lin, Oscar / McKenney, Jesse K / Montironi, Rodolfo / Paner, Gladell P / Al-Ahmadie, Hikmat A / Algaba, Ferran / Ali, Syed / Alvarado-Cabrero, Isabel / Bubendorf, Lukas / Cheng, Liang / Cheville, John C / Kristiansen, Glen / Cote, Richard J / Delahunt, Brett / Eble, John N / Genega, Elizabeth M / Gulmann, Christian / Hartmann, Arndt / Langner, Cord / Lopez-Beltran, Antonio / Magi-Galluzzi, Cristina / Merce, Jorda / Netto, George J / Oliva, Esther / Rao, Priya / Ro, Jae Y / Srigley, John R / Tickoo, Satish K / Tsuzuki, Toyonori / Umar, Saleem A / Van der Kwast, Theo / Young, Robert H / Soloway, Mark S. ·Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA. · Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA. · Department of Pathology, Johns Hopkins Hospital, Baltimore, MD, USA. · Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA. · Department of Pathology, University of California San Diego, San Diego, CA, USA. · Department of Pathology, Cleveland Clinic Foundation, Cleveland, OH, USA. · Section of Pathological Anatomy, Polytechnic University of Medicine, United Hospitals, Ancona, Italy. · Department of Pathology, University of Chicago, Chicago, IL, USA. · Pathology Section, Fundacio Puigvert, Universitat Autónoma de Barcelona, Barcelona, Spain. · Department of Pathology, Mexican Oncology Hospital, Mexico City, Mexico. · Institute of Pathology, University Hospital Basel, Basel, Switzerland. · Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA. · Institute of Pathology, University Hospital Bonn, Bonn, Germany. · Department of Pathology, University of Miami Miller School of Medicine, Miami, FL, USA. · Department of Pathology, Wellington School of Medicine and Health Sciences, University of Otago, Wellington, New Zealand. · Department of Pathology and Laboratory Medicine, Tufts Medical Center, Boston, MA, USA. · Department of Pathology, Beaumont Hospital, Dublin, Ireland. · Institute of Pathology, University Erlangen-Nürnberg, Erlangen, Germany. · Institute of Pathology, Medical University Graz, Graz, Austria. · Unit of Anatomical Pathology, Cordoba University Medical School, Faculty of Medicine, Cordoba, Spain. · James Homer Wright Pathology Laboratories, Department of Pathology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA. · Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX, USA. · Department of Pathology and Genomic Medicine, The Methodist Hospital Physician Organization, Weill Cornell Medical College of Cornell University, Houston, TX, USA. · Department Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada. · Department of Pathology, Japanese Red Cross Nagoya Daini Hospital, Nagoya, Japan. · Department of Urology, University of Miami Miller School of Medicine, Miami, FL, USA. ·Mod Pathol · Pubmed #25412849.

ABSTRACT: The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a 'Pathology of Bladder Cancer Work Group,' have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting.

2 Article Micropapillary urothelial carcinoma: evaluation of HER2 status and immunohistochemical characterization of the molecular subtype. 2018

Zinnall, Ulrike / Weyerer, Veronika / Compérat, Eva / Camparo, Philippe / Gaisa, Nadine T / Knuechel-Clarke, Ruth / Perren, Aurel / Lugli, Alessandro / Toma, Marieta / Baretton, Gustavo / Kristiansen, Glen / Wirtz, Ralph M / Cheng, Liang / Wullich, Bernd / Stoehr, Robert / Hartmann, Arndt / Bertz, Simone. ·Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin Institute for Medical Systems Biology, 13125 Berlin, Germany. · Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany. Electronic address: veronika.weyerer@uk-erlangen.de. · Department of Pathology, Hôpital Tenon, Assistance Publique-Hôpitaux de Paris, UPMC Paris VI, 75020 Paris, France. · Centre de Pathologie Amiens Picardie, 80000 Amiens, France. · Institute of Pathology, RWTH Aachen University, 52074 Aachen, Germany. · Institute of Pathology, University of Bern, 3008 Bern, Switzerland. · Institute of Pathology, University Hospital Carl Gustav Carus, 01307 Dresden, Germany. · Institute of Pathology, University Hospital Bonn, 53127 Bonn, Germany. · STRATIFYER Molecular Pathology GmbH, 50935 Cologne and Institute of Pathology at The St Elisabeth Hospital Köln-Hohenlind, 50935 Cologne, Germany. · Department of Pathology and Laboratory Medicine and Urology, Indiana University School of Medicine, Indianapolis, IN 46202, USA. · Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany. · Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, 91054 Erlangen, Germany. ·Hum Pathol · Pubmed #29885409.

ABSTRACT: Comprehensive molecular analyses of urothelial bladder cancer (UBC) have defined distinct subtypes with potential therapeutic implications. In this study, we focused on micropapillary urothelial carcinoma (MPUC), an aggressive, histomorphologically defined rare variant. Apart from genetic alterations shared with conventional UBC, alterations of the HER2 gene have been reported in higher frequencies. However, only small cohorts of MPUCs have been analyzed, and the real impact is still unclear. We collected a cohort of 94 MPUCs and immunohistochemically tested HER2, basal (CD44, CK5, EGFR, p63) and luminal (CD24, FOXA1, GATA3, CK20) markers to allocate MPUC to a molecular subtype. Additionally, HER2 amplification status was assigned by chromogenic in situ hybridization. Sanger sequencing of exon 4 and 8 was used to test for HER2 mutations. Kruskal-Wallis test was calculated to compare marker distribution between proportions of the MPUC component. HER2 2+/3+ staining scores were identified in 39.6% of 91 analyzed MPUCs and were not differentially distributed among the proportion of the MPUC component (P = .89). Additionally, CISH analysis revealed 30% of HER2-amplified tumors independently of the MPUC fraction. In 6/90 evaluable MPUCs, a p.S310F HER2 mutation was detected. Overexpression of luminal markers was observed in the majority of MPUC. Our investigations of the largest cohort of analyzed MPUC demonstrate that HER2 overexpression and amplifications are common genetic alterations and identification of overexpressed luminal markers allows subclassification to the luminal subtype. These findings highlight the need of histomorphological recognition of MPUC and analysis of HER2 status and the luminal molecular subtype for potential targeted therapeutic strategies.

3 Article The Contrasting Role of the Mediator Subunit MED30 in the Progression of Bladder Cancer. 2017

Syring, Isabella / Weiten, Richard / Müller, Tim / Schmidt, Doris / Steiner, Susanne / Kristiansen, Glen / Müller, Stefan C / Ellinger, Jörg. ·Clinic for Urology and Paediatric Urology, University Hospital of Bonn, Bonn, Germany isabella.syring@ukbonn.de. · Clinic for Urology and Paediatric Urology, University Hospital of Bonn, Bonn, Germany. · Institute of Pathology, University Hospital of Bonn, Bonn, Germany. ·Anticancer Res · Pubmed #29187445.

ABSTRACT: BACKGROUND/AIM: The Mediator complex is a key regulator of gene transcription, and several studies have demonstrated altered expression of particular subunits in diverse human diseases, especially cancer. To date, nothing is known about the role of MED30 in bladder cancer. MATERIALS AND METHODS: We, therefore, performed an RNA expression and survival analysis of the subunit MED30 in 537 samples of bladder cancer by using the database cBioPortal. To validate these data on the protein level, we practiced immunohistochemical staining against MED30 on a tissue microarray containing 210 samples of all tumour stages and performed survival analyses. For functional analysis, the siRNA-mediated knockdown of MED30 was performed in the cell lines T24 and TCCSUP followed by proliferation, migration, and invasion assays. RESULTS: On the mRNA and protein levels, higher expression of MED30 is associated with better patient survival. In accordance with this, advanced T- and N-stages showed lower expression of MED30. In contrast, knockdown of MED30 led to reduction of the tumour parameters proliferation, migration, and invasion in the BCa cell lines. CONCLUSION: MED30 appears to be integrated in the progression of the urothelial tumour in the bladder.

4 Article YRNA expression predicts survival in bladder cancer patients. 2017

Tolkach, Yuri / Stahl, Anna Franziska / Niehoff, Eva-Maria / Zhao, Chenming / Kristiansen, Glen / Müller, Stefan Cajetan / Ellinger, Jörg. ·Institute of Pathology, University Hospital Bonn, Bonn, Germany. · Department of Urology, University Hospital Bonn, Bonn, Germany. · Department of Urology, University Hospital Bonn, Bonn, Germany. joerg.ellinger@ukbonn.de. ·BMC Cancer · Pubmed #29126388.

ABSTRACT: BACKGROUND: Non-coding RNAs play an important role in human carcinogenesis. YRNAs (Ro-associated Y), a novel class of non-coding RNAs, have been identified as biomarker in various malignancies, but remain to be studied in urinary bladder cancer (BCA) patients. METHODS: The expression of all four YRNAs (RNY1, RNY3, RNY4, RNY5) was determined in archival BCA (urothelial carcinoma, n = 88) and normal urothelial bladder (n = 30) tissues using quantitative real-time PCR. Associations with clinicopathological parameters and prognostic role for overall and cancer-specific survival were analysed. RESULTS: All YRNAs were significantly downregulated in BCA tissue. A low expression of RNY1, RNY3 and RNY4 was associated with muscle-invasive BCA, lymph node metastases and advanced grade. Furthermore, expression of RNY1 and RNY3 was predictive for BCA patients' overall (also RNY4) and cancer-specific survival as estimated using Kaplan-Meier and univariate (but not multivariate) Cox regression analyses. RNY1, RNY3 and RNY4 show good discriminative ability between tumor and normal tissue, as well as between muscle-invasive and non-muscle-invasive urothelial carcinoma. CONCLUSIONS: The expression of YRNAs is altered in BCA and associated with poor prognosis. Possible diagnostic role of YRNAs should be investigated in further studies.

5 Article High grade adenocarcinoma in the ectopic prostate accompanied by a low grade adenocarcinoma in the orthotopic prostate: an unusual diagnostic pitfall. 2017

Tolkach, Yuri / Ellinger, Jörg / Müller, Stefan / Kristiansen, Glen. ·Institute for Pathology, University Hospital Bonn, Germany. · Urology Clinic, University Hospital Bonn, Germany. · Institute for Pathology, University Hospital Bonn, Germany. Electronic address: glen.kristiansen@ukbonn.de. ·Pathology · Pubmed #28830691.

ABSTRACT: -- No abstract --

6 Article Evaluation of Global Histone Acetylation Levels in Bladder Cancer Patients. 2016

Ellinger, Jörg / Schneider, Ann-Christin / Bachmann, Anne / Kristiansen, Glen / Müller, Stefan C / Rogenhofer, Sebastian. ·University Hospital Bonn, Department of Urology, Bonn, Germany joerg.ellinger@ukb.uni-bonn.de. · University Hospital Bonn, Department of Urology, Bonn, Germany. · University Hospital Bonn, Institute of Pathology, Bonn, Germany. ·Anticancer Res · Pubmed #27466500.

ABSTRACT: BACKGROUND/AIM: Alterations of global histone modification levels have been identified in various tumor entities, including bladder cancer (BCA). Our study was designed to investigate the value of global histone acetylation levels as diagnostic and prognostic biomarker for BCA patients. MATERIALS AND METHODS: A tissue microarray with formalin-fixed paraffin-embedded tissues (271 BCA and 29 normal urothelial samples) was used to determine global histone acetylation levels (histone H3 acetylation (H3Ac); histone H3 lysine 18 acetylation (H3K18Ac); histone H4 acetylation (H4Ac)). RESULTS: Global H3Ac levels were decreased in BCA patients, whereas H3K18Ac and H4Ac levels were similar in both groups. All studied histone acetylation markers were lower in muscle-invasive BCA compared to non-muscle invasive BCA and normal urothelial tissue, thereby indicating a possible prognostic relevance. CONCLUSION: Global histone acetylation levels undergo quantitative alterations during bladder cancer progression and could be helpful to identify patients at risk for early cancer recurrence.

7 Article Cytoplasmatic and Nuclear YAP1 and pYAP1 Staining in Urothelial Bladder Cancer. 2016

Latz, Stefan / Umbach, Tine / Goltz, Diane / Kristiansen, Glen / Müller, Stephan C / Ellinger, Jörg. ·Department of Urology, University Hospital Bonn, Bonn, Germany. ·Urol Int · Pubmed #26287745.

ABSTRACT: INTRODUCTION: Yes-associated protein 1 (YAP1), the nuclear effector of the Hippo pathway, plays an important role in many tumor entities. We evaluated staining and clinical significance of YAP1 and phosphorylated YAP1 (pYAP1) in urothelial bladder cancer (BCA). MATERIALS AND METHODS: We used a tissue micorarray with samples of patients with muscle-invasive bladder cancer (MIBC, n = 192), non-muscle-invasive bladder cancer (NMIBC, n = 192) and normal urothelial bladder tissue (CTRL, n = 38) to determine the immunhistochemical staining of YAP1 and pYAP1. Cytoplasmatic and nuclear levels were evaluated. The t test was used for comparative analysis. Overall survival and progression-free survival were evaluated by Kaplan-Meier estimates and the Cox proportional hazard regression model. RESULTS: Nuclear YAP1 as well as cytoplasmatic pYAP1 levels were higher in CTRL than in BCA, whereby both--NMIBC and MIBC--had lower levels than CTRL. Among patients with MIBC, cytoplasmatic YAP1 and pYAP1 staining decreased with advanced stage. YAP1 and pYAP1 staining did not correlate with the recurrence rate, progression-free, cancer-specific or overall survival. CONCLUSIONS: Immunhistochemical staining and subcellular localization of YAP1 and pYAP1 are different for BCA, NMIBC, MIBC and CTRL, indicating that the Hippo pathway is involved in urothelial carcinogenesis.

8 Article Circulating microRNAs in serum: novel biomarkers for patients with bladder cancer? 2014

Scheffer, Anna-Regina / Holdenrieder, Stefan / Kristiansen, Glen / von Ruecker, Alexander / Müller, Stefan C / Ellinger, Jörg. ·Klinik und Poliklinik für Urologie und Kinderurologie, Universitätsklinikum Bonn, Sigmund-Freud-Strasse 25, 53105, Bonn, Germany. ·World J Urol · Pubmed #23266581.

ABSTRACT: PURPOSE: Recent studies indicate that circulating microRNAs in serum/plasma are a novel class of non-invasive biomarkers with diagnostic and prognostic information. So far, circulating microRNAs have not been analyzed in patients with bladder cancer. METHODS: We collected serum from patients with non-muscle invasive bladder cancer (NMIBC), muscle invasive bladder cancer (MIBC) and non-malignant urological disease. Total RNA was isolated from 400 μl of serum using the mirVana PARIS Kit; the artificial cel-miR-39 was spiked-in prior to RNA isolation to control different RNA isolation efficiencies. Quantitative real-time PCR was applied to measure the levels of 22 microRNAs upregulated in BCA tissue (miR-15a, miR-18a, miR-21, miR-93, miR-96, miR-103, miR-130b, miR-135b, miR-141, miR-182, miR-183, miR-190, miR-191, miR-200b, miR-422b, miR-425, miR-449b, miR-601, miR-639, miR-644, miR-649 and miR-1233) in the marker identification cohort (NMIBC, n = 11, MIBC, n = 10; controls, n = 10). The most promising serum microRNAs were tested in a validation cohort (NMIBC, n = 65, MIBC, n = 61; controls, n = 105). RESULTS: The RNA recovery was similar in patients with NMIBC, MIBC and control subjects. The analysis of serum microRNA levels in the marker identification cohort indicated that serum miR-141 and miR-639 levels were increased in bladder cancer patients compared to CTRL. The analysis of these miR-141 and miR-639 in the validation cohort demonstrated that microRNA levels were similar in bladder cancer patients and control subjects. Furthermore, microRNA levels were not correlated with clinicopathological parameters (pT-stage, metastasis, grading). CONCLUSIONS: The analysis of serum miR-141 and miR-639 levels does not seem to be helpful in the diagnosis or prognosis of BCA.

9 Article An interobserver reproducibility study on invasiveness of bladder cancer using virtual microscopy and heatmaps. 2013

Compérat, Eva / Egevad, Lars / Lopez-Beltran, Antonio / Camparo, Philippe / Algaba, Ferran / Amin, Mahul / Epstein, Jonathan I / Hamberg, Hans / Hulsbergen-van de Kaa, Christina / Kristiansen, Glen / Montironi, Rodolfo / Pan, Chin-Chen / Heloir, Fabrice / Treurniet, Kilian / Sykes, Jenna / Van der Kwast, Theo H. ·Department of Pathology, Groupe Hospitalier La Pitié-Salpêtrière, Université Pierre et Marie Curie, Paris, France. ·Histopathology · Pubmed #24102813.

ABSTRACT: AIMS: The distinction between non-invasive (pTa) and invasive (pT1) non-muscle invasive bladder cancer (NMIBC) is subject to considerable interobserver variation. We aimed to generate a teaching set of images based on the diagnostic opinions of a panel of expert genitourinary pathologists. METHODS AND RESULTS: Twenty-five transurethral resection specimens initially reported as pT1 NMIBC from two university hospitals were selected on the basis of potential uncertainty of stromal invasion. Digitized slides were reviewed independently by a panel of eight genitourinary pathologists, who annotated any invasive area if present. Annotations were reviewed by the lead panel, and heatmaps of annotated areas were constructed. Reasons for discrepancies were analysed, and kappa scores were calculated to determine agreement among the eight panellists. Full agreement by the eight panellists was obtained in 11 of 25 cases (44%), with a multi-rater (Fleiss) kappa of 0.47 (P < 0.0001). After joint review of the seven discordant (agreement <75% of panellists) cases, consensus was obtained for six cases, and a teaching set of images was generated. CONCLUSIONS: Interobserver agreement among the panellists in the selected cases was moderate, but consensus could be reached in almost all cases. Heatmaps proved to be instrumental in generating a teaching set of images for standardization of histological criteria for NMIBC invasion.

10 Article Evaluation of reference genes for the analysis of serum miRNA in patients with prostate cancer, bladder cancer and renal cell carcinoma. 2012

Sanders, Imke / Holdenrieder, Stefan / Walgenbach-Brünagel, Gisela / von Ruecker, Alexander / Kristiansen, Glen / Müller, Stefan C / Ellinger, Jörg. ·Department of Urology, University Hospital Bonn, Bonn, Germany. ·Int J Urol · Pubmed #22788411.

ABSTRACT: OBJECTIVES: To identify an appropriate reference gene for the analysis of circulating micro-ribonucleic acid in patients with urological malignancies. METHODS: Serum from patients with prostate cancer (n = 24), bladder cancer (n = 24), renal cell carcinoma (n = 24) and control subjects (n = 48) was spiked with cel-miR-39, and then ribonucleic acid was isolated. Quantitative real-time polymerase chain reaction was used to determine the levels of candidate reference genes (RNU1-4, RNU6-2, SNORD43, SNORD44, SNORD48, SNORA74A, miR-let-7a-1, miR-106a). Reference gene stability was determined using the NormFinder, geNorm and comparative delta-Ct algorithm. The effect of normalization was tested with miR-21 as the target gene, as this was previously suggested to be upregulated in cancer patients' serum. RESULTS: Recovery of cel-miR-39 (mean 11.6%, range 1-56%) was similar in control subjects and cancer patients. SNORD44 and SNORD74A levels were around the detection limit of the assay and were thus omitted. All remaining candidates showed satisfying stability; SNORD43 was the most stable reference gene using all three algorithms. A combination of two genes (SNORD43, RNU1-4) increases the stability somewhat. The level of miR-21 was similar in cancer patients and healthy controls, irrespective of the normalization strategy. CONCLUSIONS: SNORD43 is a suitable reference gene for the analysis of circulating micro-ribonucleic acid in patients with urological malignancies. Our study questions the suitability of miR-21 as a biomarker for uro-oncological patients.

11 Article CD24 offers a therapeutic target for control of bladder cancer metastasis based on a requirement for lung colonization. 2011

Overdevest, Jonathan B / Thomas, Shibu / Kristiansen, Glen / Hansel, Donna E / Smith, Steven C / Theodorescu, Dan. ·Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA. ·Cancer Res · Pubmed #21482678.

ABSTRACT: Metastasis is lethal in most bladder cancer patients. Expression of CD24, a glycosyl phosphatidylinositol (GPI)-linked sialoglycoprotein and cancer stem cell marker, is associated with metastatic progression in multiple cancer types, yet the role of CD24 in this process remains unclear. While developing a murine model of human metastatic bladder cancer, we observed that tumor cell CD24 expression correlated with a propensity to metastasize to the lung. Our immunohistochemical evaluation of 60 paired primary and metastatic human bladder cancer samples revealed increased intensity (P < 0.001) and frequency (P < 0.001) of CD24 expression in metastases. To directly evaluate the role of CD24 in metastatic colonization, we manipulated CD24 expression in human bladder cancer cell lines using short hairpin RNA depletion, cDNA overexpression, and fluorescence-activated cell sorting selection. Although suppression of CD24 reduced acute tumor cell retention in the lungs of mice inoculated intravenously with cancer cells, this differential retention was no longer apparent after 24 hours, prompting us to evaluate the role of CD24 in lung colonization. Here, CD24 was found necessary for subsequent development of lung metastases. We next treated clinically detectable lung metastases in mice with anti-CD24 antibody and observed reduced tumor growth and prolonged survival. These findings suggest that CD24 is a lynchpin of metastatic progression and a promising therapeutic target for antimetastatic therapy.

12 Article Prognostic accuracy of individual uropathologists in noninvasive urinary bladder carcinoma: a multicentre study comparing the 1973 and 2004 World Health Organisation classifications. 2010

May, Matthias / Brookman-Amissah, Sabine / Roigas, Jan / Hartmann, Arndt / Störkel, Stephan / Kristiansen, Glen / Gilfrich, Christian / Borchardt, Roman / Hoschke, Bernd / Kaufmann, Olaf / Gunia, Sven. ·Department of Urology, Clinic St. Elisabeth, Straubing, Germany. ·Eur Urol · Pubmed #19346063.

ABSTRACT: BACKGROUND: Grading of noninvasive papillary urinary bladder carcinoma (PUC) is routinely performed in clinical oncologic practice; however, reports regarding diagnostic and prognostic accuracy are contradictory. OBJECTIVE: To compare the 1973 and 2004 World Health Organisation (WHO) classifications in terms of interobserver variability and prognostic implications. DESIGN, SETTING, AND PARTICIPANTS: Two hundred PUC were retrospectively reviewed by four independent expert genitourinary pathologists blinded with respect to patient identity and clinical outcome. Tumour grading was assigned according to the 1973 and 2004 WHO classifications. Surveying a mean postsurgical follow-up of 71.8 mo (range: 18-163 mo), clinical outcome in terms of recurrence-free and progression-free survival was recorded for all patients. INTERVENTION: All of the patients underwent transurethral resection of the bladder. MEASUREMENTS: The generalised κ (kappa statistic) for interobserver variability was calculated, and Kaplan-Meier analysis as well as univariate regression analysis were performed to evaluate prognostic implications in terms of recurrence and progression rates. RESULTS AND LIMITATIONS: During the follow-up, a total of 84 (42%) patients experienced recurrence, whereas another 18 (9%) patients featured disease progression. Owing to the rare presence of papillary urothelial neoplasms of low malignant potential (PUNLMP) in our cohort (0-3.5%), the 2004 WHO classification approached a two-tier system (low and high grade), which showed less interobserver variability than the 1973 classification (κ: 0.30-0.52 vs 0-0.37, respectively). In comparing the power of both classifications to separate indolent from aggressive PUC, striking pathologist-dependent differences became apparent. CONCLUSIONS: Both WHO classifications for grading of PUC suffer from substantial interobserver variability, with the 2004 WHO classification showing less interobserver variability. Stark differences in the prognostic power of the individual grading approaches were also found. These significant differences in the individual interpretation of the WHO grading schemes for noninvasive PUC highlight the necessity of better-defined criteria for conventional tumour grading; otherwise, the subdivision into prognostically different groups by conventional histomorphology might remain of limited value.

13 Article Detection of urothelial bladder cancer cells in voided urine can be improved by a combination of cytology and standardized microsatellite analysis. 2009

Wild, Peter J / Fuchs, Thomas / Stoehr, Robert / Zimmermann, Dieter / Frigerio, Simona / Padberg, Barbara / Steiner, Inbal / Zwarthoff, Ellen C / Burger, Maximilian / Denzinger, Stefan / Hofstaedter, Ferdinand / Kristiansen, Glen / Hermanns, Thomas / Seifert, Hans-Helge / Provenzano, Maurizio / Sulser, Tullio / Roth, Volker / Buhmann, Joachim M / Moch, Holger / Hartmann, Arndt. ·Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. peter.wild@usz.ch ·Cancer Epidemiol Biomarkers Prev · Pubmed #19454613.

ABSTRACT: PURPOSE: To evaluate molecular and immunohistochemical markers to develop a molecular grading of urothelial bladder cancer and to test these markers in voided urine samples. EXPERIMENTAL DESIGN: 255 consecutive biopsies from primary bladder cancer patients were evaluated on a tissue microarray. The clinical parameters gender, age, adjacent carcinoma in situ, and multifocality were collected. UroVysion fluorescence in situ hybridization (FISH) was done. Expression of cytokeratin 20, MIB1, and TP53 was analyzed by immunohistochemistry. Fibroblast growth factor receptor 3 (FGFR3) status was studied by SNaPshot mutation detection. Results were correlated with clinical outcome by Cox regression analysis. To assess the predictive power of different predictor subsets to detect high grade and tumor invasion, logistic regression models were learned. Additionally, voided urine samples of 119 patients were investigated. After cytologic examination, urine samples were matched with their biopsies and analyzed for loss of heterozygosity (LOH), FGFR3 mutation, polysomy, and p16 deletion using UroVysion FISH. Receiver operator characteristic curves for various predictor subsets were plotted. RESULTS: In biopsies, high grade and solid growth pattern were independent prognostic factors for overall survival. A model consisting of UroVysion FISH and FGFR3 status (FISH + FGFR3) predicted high grade significantly better compared with a recently proposed molecular grade (MIB1 + FGFR3). In voided urine, the combination of cytology with LOH analysis (CYTO + LOH) reached the highest diagnostic accuracy for the detection of bladder cancer cells and performed better than cytology alone (sensitivity of 88.2% and specificity of 97.1%). CONCLUSIONS: The combination of cytology with LOH analysis could reduce unpleasant cystoscopies for bladder cancer patients.