Sensitive detection of transitional cell carcinoma of the bladder by microsatellite analysis of cells exfoliated in urine

Citation
D. Seripa et al., Sensitive detection of transitional cell carcinoma of the bladder by microsatellite analysis of cells exfoliated in urine, INT J CANC, 95(6), 2001, pp. 364-369
Citations number
56
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
INTERNATIONAL JOURNAL OF CANCER
ISSN journal
00207136 → ACNP
Volume
95
Issue
6
Year of publication
2001
Pages
364 - 369
Database
ISI
SICI code
0020-7136(20011120)95:6<364:SDOTCC>2.0.ZU;2-M
Abstract
Transitional cell carcinoma (TCC) is the most common bladder tumor. Urine c ytology can identify most high-grade tumors but sensitivity is lower if one includes lesions of all grades. Microsatellite marker alterations have bee n found in many tumor types including bladder cancer and have been used to detect cancer cells in body fluids including urine. The aim of our study is to further evaluate feasibility and sensitivity of microsatellite analysis to detect bladder cancer cells in urine. We studied 55 individuals: 21 wit h symptoms suggestive of bladder cancer, 23 patients with previous history of TCC and I I healthy subjects. Genomic DNA was extracted from blood lymph ocytes, urine sediment, bladder washings and tumor or normal bladder mucosa . Twenty highly informative microsatellite markers were analyzed for loss o f heterozigosity (LOH) and microsatellite instability (MIN) by polymerase c hain reaction. Microsatellite analysis of urine identified 33 of 34 (97%) p atients with either primary or tumor recurrence, whereas urine cytology ide ntified 27 of 34 (79%) patients (p = 0.0001). Detection of microsatellite a bnormalities improved the sensitivity of detecting low-grade and/or stage b ladder tumor: from 75-95% for grades G1-G2 and from 75-100% for pTis-pTa tu mors. Bladder washings from 25 patients were also analyzed, and in all case s results were identical to those obtained from voided urine. None of the 1 6 patients without evidence of TCC showed LOH and/or MIN in urine samples o r bladder washings. Interestingly, in a patient with persistent bladder muc osa abnormalities, microsatellite alterations were demonstrated 8 months be fore the histopathologic diagnosis of tumor recurrence. These results furth er indicate that microsatellite marker analysis is more sensitive than conv entional urine cytology in detecting bladder cancer cells in urine and repr esents a potential clinical tool for monitoring patients with low-grade/sta ge TCC. (C) 2001 Wiley-Liss, Inc.