Quantitative Loss of Heterozygosity Analysis for Urothelial Carcinoma Detection and Prognosis

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• 作者：Delphine Collin-Chavagnac ; Christophe Març ; ais ; Stephane Billon ; Franç ; oise Descotes ; Eric Piaton ; Myriam Decaussin ; Claire Rodriguez-Lafrasse ; Alain Ruffion
• 刊名：Urology
• 出版年：2010
• 出版时间：August 2010
• 年：2010
• 卷：76
• 期：2
• 页码：515.e1-515.e7
• 全文大小：193 K

文摘

Objectives

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.