PMID- 19454613 OWN - NLM STAT- MEDLINE DCOM- 20090908 LR - 20161125 IS - 1538-7755 (Electronic) IS - 1055-9965 (Linking) VI - 18 IP - 6 DP - 2009 Jun TI - Detection of urothelial bladder cancer cells in voided urine can be improved by a combination of cytology and standardized microsatellite analysis. PG - 1798-806 LID - 10.1158/1055-9965.EPI-09-0099 [doi] AB - 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. FAU - Wild, Peter J AU - Wild PJ AD - Institute of Surgical Pathology, University Hospital Zurich, Zurich, Switzerland. peter.wild@usz.ch FAU - Fuchs, Thomas AU - Fuchs T FAU - Stoehr, Robert AU - Stoehr R FAU - Zimmermann, Dieter AU - Zimmermann D FAU - Frigerio, Simona AU - Frigerio S FAU - Padberg, Barbara AU - Padberg B FAU - Steiner, Inbal AU - Steiner I FAU - Zwarthoff, Ellen C AU - Zwarthoff EC FAU - Burger, Maximilian AU - Burger M FAU - Denzinger, Stefan AU - Denzinger S FAU - Hofstaedter, Ferdinand AU - Hofstaedter F FAU - Kristiansen, Glen AU - Kristiansen G FAU - Hermanns, Thomas AU - Hermanns T FAU - Seifert, Hans-Helge AU - Seifert HH FAU - Provenzano, Maurizio AU - Provenzano M FAU - Sulser, Tullio AU - Sulser T FAU - Roth, Volker AU - Roth V FAU - Buhmann, Joachim M AU - Buhmann JM FAU - Moch, Holger AU - Moch H FAU - Hartmann, Arndt AU - Hartmann A LA - eng PT - Journal Article DEP - 20090519 PL - United States TA - Cancer Epidemiol Biomarkers Prev JT - Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology JID - 9200608 RN - 0 (Biomarkers, Tumor) RN - EC 2.3.2.27 (MIB1 ligase, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 3) SB - IM EIN - Cancer Epidemiol Biomarkers Prev. 2010 Feb;19(2):629-30 MH - Biomarkers, Tumor/*genetics/*urine MH - *Cytological Techniques MH - DNA Mutational Analysis MH - Female MH - Humans MH - Immunohistochemistry MH - In Situ Hybridization, Fluorescence MH - Kaplan-Meier Estimate MH - Loss of Heterozygosity MH - Male MH - Microsatellite Repeats/*genetics MH - Receptor, Fibroblast Growth Factor, Type 3/biosynthesis/genetics MH - Sensitivity and Specificity MH - Tissue Array Analysis MH - Ubiquitin-Protein Ligases/metabolism MH - Urinary Bladder Neoplasms/diagnosis/*genetics/*urine EDAT- 2009/05/21 09:00 MHDA- 2009/09/09 06:00 CRDT- 2009/05/21 09:00 PHST- 2009/05/21 09:00 [entrez] PHST- 2009/05/21 09:00 [pubmed] PHST- 2009/09/09 06:00 [medline] AID - 1055-9965.EPI-09-0099 [pii] AID - 10.1158/1055-9965.EPI-09-0099 [doi] PST - ppublish SO - Cancer Epidemiol Biomarkers Prev. 2009 Jun;18(6):1798-806. doi: 10.1158/1055-9965.EPI-09-0099. Epub 2009 May 19.