Numeric aberration of chromosome 17 is strongly correlated with p53 overexpression, tumor proliferation and histopathology in human bladder cancer.
BACKGROUND
This study investigated the relationships between the numeric aberrations of chromosome 17 and p53 expression, the proliferating cell nuclear antigen labeling index (PCNA-LI) and histopathology, to determine their prognostic significance in bladder cancer.


METHODS
Using in situ hybridization (ISH) with a biotin-labeled chromosome-specific DNA probe, the copy number of pericentromeric sequences in chromosome 17 were detected within interphase nuclei in formalin-fixed paraffin-embedded sections from 59 nonmetastasized transitional cell carcinomas (TCCs) of the urinary bladder. Expression of p53 and PCNA-LI were determined in serial sections by an immunohistochemical method.


RESULTS
The percentage of hyperdiploid cells for chromosome 17 correlated with p53 overexpression (P< 0.002), PCNA-LI (P< 0.002), increasing tumor grade (P< 0.002) and advanced pathologic stage (P< 0.002). The average percentage of hyperdiploid cells was lower in tumors with negative p53 expression than in tumors with p53 overexpression (P< 0.002). Also, more polysomic TCCs were found in muscle-invasive than in superficial cases (P< 0.01 ), and there was a difference in both p53 overexpression or PCNA-LI between disomic and polysomic TCCs (P< 0.01). Patients with chromosome 17 disomic tumors showed less frequent tumor progression than patients with polysomic tumors (P< 0.05). However, chromosome 17 polysomy was an independent prognostic indicator only for patient survival (P< 0.05).


CONCLUSIONS
The occurrence and extent of numeric aberrations of chromosome 17 may be associated with the evolution of aggressive growth in TCC and may be a useful indicator for survival.
Department of Urology, Fukui Medical University, Japan.
B
B
Li
H
H
Kanamaru
S
S
Noriki
M
M
Fukuda
K
K
Okada
D000368:Aged; D000369:Aged, 80 and over; D002503:Centromere / Q000235:genetics; D002869:Chromosome Aberrations; D002886:Chromosomes, Human, Pair 17; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D007399:Interphase / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D011379:Prognosis; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality
D018809:Proliferating Cell Nuclear Antigen; D016159:Tumor Suppressor Protein p53