PMID- 23172833
OWN - NLM
STAT- MEDLINE
DCOM- 20130712
LR  - 20220331
IS  - 1934-6638 (Electronic)
IS  - 1934-662X (Linking)
VI  - 121
IP  - 5
DP  - 2013 May
TI  - Combined application of cytology and molecular urine markers to improve the 
      detection of urothelial carcinoma.
PG  - 252-60
LID - 10.1002/cncy.21247 [doi]
AB  - BACKGROUND: The sensitivity of cytology for the detection of urothelial carcinoma 
      (UC) is limited. Newer methods such as fluorescence in situ hybridization (FISH), 
      immunocytology (uCyt+), and protein markers have been developed to improve 
      urine-based detection of UC. As only little is known regarding the combined 
      application of these markers, we investigated whether combinations of 4 of the 
      most broadly available tests (cytology, FISH, uCyt+, and nuclear matrix protein 
      22 [NMP22-ELISA]) may improve their diagnostic performance. METHODS: The study 
      was comprised of 808 patients who were suspected of having UC. All patients 
      underwent urethrocystoscopy and upper urinary tract imaging and, in the case of 
      positive findings, transurethral resection/biopsy. FISH, uCyt+, cytology, and 
      NMP22-ELISA were performed in all patients. RESULTS: UC was diagnosed in 115 
      patients (14.2%). Cytology and FISH were found to be the single tests with the 
      best overall performance (area under the curve [AUC], 0.78/0.79). Combinations of 
      2, 3, and 4 markers were found to increase the AUC to various extents compared 
      with the use of single markers. Combining cytology and FISH improved the 
      sensitivity and performance (AUC, 0.83) compared with the single tests and 
      identified 12 tumors that were not detected by cytology alone. The percentage of 
      WHO grade 3/carcinoma in situ tumors not detected by cytology was reduced by 
      62.5% when FISH was performed in cytology-negative patients. The addition of 
      uCyt+ as a third test further improved performance (AUC, 0.86), whereas the 
      addition of NMP22-ELISA was not found to have any additional influence on the 
      performance of the test combination. CONCLUSIONS: The results of the current 
      study support the combined use of urine markers and may form the basis of further 
      studies investigating whether risk stratification based on urine marker 
      combinations may individualize diagnostic algorithms and the surveillance of 
      patients suspected of having UC.
CI  - Copyright (c) 2012 American Cancer Society.
FAU - Todenhofer, Tilman
AU  - Todenhofer T
AD  - Department of Urology, University Hospital Tubingen, Tubingen, Germany.
FAU - Hennenlotter, Jorg
AU  - Hennenlotter J
FAU - Esser, Michael
AU  - Esser M
FAU - Mohrhardt, Sarah
AU  - Mohrhardt S
FAU - Tews, Veronika
AU  - Tews V
FAU - Aufderklamm, Stefan
AU  - Aufderklamm S
FAU - Gakis, Georgios
AU  - Gakis G
FAU - Kuehs, Ursula
AU  - Kuehs U
FAU - Stenzl, Arnulf
AU  - Stenzl A
FAU - Schwentner, Christian
AU  - Schwentner C
LA  - eng
PT  - Journal Article
DEP - 20121121
PL  - United States
TA  - Cancer Cytopathol
JT  - Cancer cytopathology
JID - 101499453
RN  - 0 (Nuclear Proteins)
RN  - 0 (nuclear matrix protein 22)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Transitional Cell/*diagnosis/genetics/urine
MH  - Cytodiagnosis/*methods
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Nuclear Proteins/analysis
MH  - Reproducibility of Results
MH  - Sensitivity and Specificity
MH  - Urinary Bladder Neoplasms/*diagnosis/genetics/urine
MH  - Urine/*cytology
MH  - Young Adult
EDAT- 2012/11/23 06:00
MHDA- 2013/07/16 06:00
CRDT- 2012/11/23 06:00
PHST- 2012/08/08 00:00 [received]
PHST- 2012/09/03 00:00 [revised]
PHST- 2012/09/19 00:00 [accepted]
PHST- 2012/11/23 06:00 [entrez]
PHST- 2012/11/23 06:00 [pubmed]
PHST- 2013/07/16 06:00 [medline]
AID - 10.1002/cncy.21247 [doi]
PST - ppublish
SO  - Cancer Cytopathol. 2013 May;121(5):252-60. doi: 10.1002/cncy.21247. Epub 2012 Nov 
      21.