Status of the p53, p16, RB1, and HER-2 genes and chromosomes 3, 7, 9, and 17 in advanced bladder cancer: correlation with adjacent mucosa and pathological parameters.
OBJECTIVE
To evaluate a panel of well known genetic alterations for frequency of changes in bladder cancer that could be considered genomic instability determinants or adjunctive prognostic predictors.


METHODS
Fluorescence in situ hybridisation analysis was performed to evaluate chromosomes 3, 7, 9, and 17 and the 9p21 (p16), 17p13.1 (p53), 13q14 (RB1), and 17q11.2 (HER-2) chromosomal loci in 48 muscle invasive bladder cancer specimens and the adjacent normal mucosa.


RESULTS
There were significant differences between the frequency of chromosome 7 monosomy/polysomy and 17 monosomy in the two groups (tumours and adjacent mucosa) (p = 0.004, p = 0.037, and p = 0.015, respectively). There were no differences in the frequency of gene deletions between tumours and the adjacent mucosa. 17q11.2 amplification was found in 14.5% of tumours examined, but not in the non-malignant epithelium. Chromosome 3, 7, and 17 monosomy and the RB1 heterozygous deletion were significantly associated with stage T3-4 (p = 0.03, p = 0.04, p = 0.04, and p = 0.03, respectively).


CONCLUSIONS
These results demonstrate the importance of chromosomes 3, 7, and 17 and gene alterations in bladder cancer progression, highlighting their usefulness as prognostic markers. Larger studies with longterm follow up of these patients are needed to determine the validity and clinical relevance of these genetic findings, and molecular prognostic markers should be incorporated into phase II and III trials to define their roles in predicting clinical outcome.
Gallucci
M
M
Department of Urology, Regina Elena Cancer Institute, Via Elio Chianesi, 53, 00144 Rome, Italy. cianciulli@ifo.it
Guadagni
F
F
Marzano
R
R
Leonardo
C
C
Merola
R
R
Sentinelli
S
S
Ruggeri
E M
EM
Cantiani
R
R
Sperduti
I
I
Lopez
F de la Iglesia
Fde L
Cianciulli
A M
AM
D002877:Chromosomes, Human / Q000235:genetics*; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D005784:Gene Amplification / Q000235:genetics; D017353:Gene Deletion; D018734:Genes, erbB-2 / Q000235:genetics; D019942:Genes, p16; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods; D019901:Locus Control Region; D009092:Mucous Membrane / Q000737:chemistry; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics*; D016160:Retinoblastoma Protein / Q000235:genetics; D018709:Statistics, Nonparametric; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
D009363:Neoplasm Proteins; D016160:Retinoblastoma Protein; D016159:Tumor Suppressor Protein p53