Quantitative loss of heterozygosity analysis for urothelial carcinoma detection and prognosis.
OBJECTIVE
To evaluate loss of heterozygosity (LOH) using microsatellite polymorphism analysis as a diagnostic and prognostic marker at the time of transurethral resection and as a follow-up marker preceding cystoscopic evidence of recurrence compared with cytology.


METHODS
A total of 127 urothelial carcinoma (UC) patients were included. Tumors were staged and graded according to the International Union Against Cancer-tumor, node, metastases system and to the 2004 World Health Organization classification. LOH urinalysis was performed using 8 markers and marker-specific LOH thresholds. Thirty control samples, obtained from healthy volunteers, were used to determine the positive cut-off for each marker.


RESULTS
LOH was significantly more sensitive than cytology in low-grade (64.8% vs 38.5%, P <.001) and low-stage UC (68.6% vs 45.5%, P <.001). The cumulative sensitivity of cytology and LOH reached 74.7% (P <.001) for low-grade and 80.2% (P <.001) for low-stage tumors. Both urinary LOH at TP53 and chromosome 9p markers were associated with an increased risk of recurrence (relative risk = 1.73 [1.30-2.31], P = .0002) and occurred more frequently in the initial urine samples of patients who later relapsed from primary tumors (36.4% vs 0.0%, P <.05 and 57.6% vs 15.8%, P = .0001). Among 32 relapse patients, LOH was positive alongside cystoscopy in 25 of 32 cases and tested positive before cystoscopy detected recurrence in a further 5 of 25 cases.


CONCLUSIONS
UC diagnosis and monitoring would greatly benefit from supplementing conventional cytology with LOH urinalysis, using a panel of 8 microsatellite markers with specific threshold levels. Given the limitations of both cystoscopy and cytology, novel molecular markers are needed for detection and follow-up of UC.
Collin-Chavagnac
Delphine
D
Service de Biochimie et Biologie Moléculaire Sud, Centre Hospitalier Universitaire Lyon Sud, Chemin du Grand Revoyet, Pierre Bénite, Hospices Civils de Lyon, France. delphine.collin_chavagnac@bbox.fr
Marçais
Christophe
C
Billon
Stephane
S
Descotes
Françoise
F
Piaton
Eric
E
Decaussin
Myriam
M
Rodriguez-Lafrasse
Claire
C
Ruffion
Alain
A
D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D001749:Urinary Bladder Neoplasms / Q000235:genetics*