title: Prospective evaluation of genetic abnormalities and telomerase expression in exfoliated urinary cells for bladder cancer detection.
abstract: OBJECTIVE
  To evaluate alternative procedures to cytoscopic examination we prospectively compared noninvasive procedures for detecting bladder cancer namely cytology, loss of heterozygosity (LOH), microsatellite instability and human telomerase catalytic subunit reverse transcriptase (hTERT) messenger (m) RNA detection.
  
  
  METHODS
  Specificity and cutoff values were established in the blood and urine sediment of 50 controls. Sensitivity was analyzed in the urine and tissue samples of 50 patients with bladder cancer. The diagnosis was established by cystoscopic and histological examination. Genomic alterations were studied using a panel of 24 microsatellite markers to detect LOH events, while 3 additional mononucleotide repeats were analyzed for microsatellite instability detection. Telomerase expression was detected in urinary cells by nested RT-polymerase chain reaction amplification of hTERT mRNA. All techniques were compared by cytological examination.
  
  
  RESULTS
  Sensitivity and specificity were 31% and 100% for cytological testing, 96% and 100% for LOH, and 75% and 69% for RT-polymerase chain reaction of hTERT, respectively. No alteration was detected on microsatellite instability analysis in urine or tumor tissue cells. Using only the 5 markers most strongly associated with bladder cancer selected by logistic regression analysis, namely ABL1, IFNa, D9S12, MJD58 and D18S364, LOH test sensitivity slightly decreased to 90%.
  
  
  CONCLUSIONS
  Urinary LOH analysis was the most sensitive and specific method for bladder cancer detection and it appeared less dependent on urine sediment quality. The logistic regression score may be an interesting complement to cystoscopy. The specificity of hTERT mRNA detection was incomplete since false-positives were observed in 31% of cases. Absent microsatellite instability in our cohort showed that these genomic alterations are not present at the early step of bladder cancer.
authors.affiliation: Laboratoire d'Histologie, Biologie Tumorale et Génétique Moléculaire, Service d'Urologie, Hôpital TENON, Paris, France.
authors.forename: Manuel
authors.initials: M
authors.lastname: Neves
authors.forename: Calin
authors.initials: C
authors.lastname: Ciofu
authors.forename: Frédérique
authors.initials: F
authors.lastname: Larousserie
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Fleury
authors.forename: Mathilde
authors.initials: M
authors.lastname: Sibony
authors.forename: Antoine
authors.initials: A
authors.lastname: Flahault
authors.forename: Florent
authors.initials: F
authors.lastname: Soubrier
authors.forename: Bernard
authors.initials: B
authors.lastname: Gattegno
mesh_terms: D020134:Catalytic Domain / Q000235:genetics; D004268:DNA-Binding Proteins; D006801:Humans; D016015:Logistic Models; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D011446:Prospective Studies; D012333:RNA, Messenger / Q000032:analysis; D012680:Sensitivity and Specificity; D019098:Telomerase / Q000032:analysis / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000235:genetics; D014556:Urine / Q000166:cytology* / Q000502:physiology
chemical_list: D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D019098:Telomerase