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
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.