[Microsatellite analysis in exfoliated cells from urinary sediment. Its utility for the detection of bladder cancer. Comparison with urinary cytology].

INTRODUCTION

Taking into account the precocity of the genetic alterations in the carcinogenesis of the bladder tumors, the valuation of these changes at a level of 9p 21-22 by means of microsatellite markers could be useful for the diagnostic and follow-up.

PURPOSE

To evaluate the use of microsatellite markers and the utility of loss of heterozigosity (LOH) and microsatellite instability (MSI) in exfoliated cells from urine sediment. This observation offers the possibility of tumor detection by examining the DNA of urinary sediment.

MATERIALS AND METHODS

We amplified with PCR the DNA of urine and blood samples from 160 patients with bladder cancer. We analysed LOH/MSI in cells from urinary sediment using four microsatellite markers of 9p 21-22 (D9S747-D9S171-D9S162-IFNA) and one from chromosome 4 (D4S243). The urinary cytology was used as comparative method and histological examination of tissue obtained by transurethral resection (TUR) as reference diagnostic. We calculated the sensitivity and specificity of this method and if there was some correlation between stage and grade tumoral.

RESULTS

We could use 150 samples correctly. In 111 samples we found LOH/MSI (sensitivity 74%). The cytology was positive only in 60 patients (sensitivity 40%). We found a bigger number of microsatellite alterations (AM) in superficial tumors (sensibility 77.3% vs. 28.8% for the cytology) and these were significant when comparing tumors GI-II vs. GIII (MSI p < 0.001--LOH p < 0.004). The marker with more sensibility was D4S243 with 40%. One patient with prostate carcinoma and another one with chronic cystitis gave false positive results.

CONCLUSIONS

The study of LOH/MSI in bladder tumors with 5 microsatellites markers, according to our results showed a sensibility of 74%. The biggest number in LOH/MSI was found in superficial tumors and GI-GII tumors. Although we cannot discard the cystoscopy study in the diagnostic and follow-up, the sensitivity of the urine cytology is better and could be one alternative diagnostic as a non-invasive procedure.