Prognostic role of loss of heterozygosity on chromosome 18 in patients with low-risk nonmuscle-invasive bladder cancer: results from a prospective study.
BACKGROUND
Somatic alterations on chromosome (Chr) 18q21-23, such as loss of heterozygosity (LOH), have been indicated as a critical step in bladder carcinogenesis. The aim of this study was to evaluate the prognostic role of LOH on Chr 18q21-23 in patients affected by low-grade, nonmuscle-invasive bladder cancer (NMIBC).


METHODS
A group of 108 consecutive subjects (65 affected by low-risk NMIBC and 43 controls) were selected for this prospective study. LOH on Chr 18 was assessed in the blood and urine samples. The primers used were D18S51, MBP LW, and MBP H. The data obtained were compared with follow-up information. Results were also analyzed by using artificial neural networks (ANN).


RESULTS
Out of the 65 patients with NMIBC, 38 (58.4%) showed at least one alteration on Chr 18, while 27 (41.6%) showed no alteration. In the control group, only 2 out of 43 subjects showed LOH on Chr 18. At the end of follow-up, 29 patients were alive without recurrence, while 36 had at least one recurrence. A significant correlation between LOH on Chr 18 and status at follow-up was found (P = 0.022). Kaplan-Meier curves demonstrated a significant correlation between recurrence-free status and LOH on Chr 18 (P = 0.0003). At multivariate analysis, LOH on Chr 18 (P = 0.002) and the number of lesions (P = 0.03) were identified as independent predictors of recurrence-free probability. ANN analysis confirmed the results from multivariate analysis.


CONCLUSIONS
This study highlights the role of LOH analysis on Chr 18 in improving recurrence prediction in patients affected by low-grade NMIBC.
Cai
Tommaso
T
Department of Urology, University of Florence, Florence, Italy. ktommy@libero.it
Nesi
Gabriella
G
Dal Canto
Maurizio
M
Mondaini
Nicola
N
Piazzini
Mauro
M
Bartoletti
Riccardo
R
D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000175:diagnosis*; D002887:Chromosomes, Human, Pair 18; D005260:Female; D006801:Humans; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D016571:Neural Networks, Computer; D011379:Prognosis; D011446:Prospective Studies; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis*