Correlation of allelic loss of the P53 gene and tumor grade, stage, and malignant progression in bladder cancer.
BACKGROUND
We examined loss of heterozygosity (LOH) of the P53 gene in bladder cancer, and investigated the role of the P53 gene on malignant progression of papillary tumors. In addition, the clonality of recurrent bladder cancer was examined.


METHODS
LOH of the P53 gene was analyzed in 67 bladder cancers from 47 patients. DNA was extracted from formalin-fixed, paraffin-embedded tissues, amplified by the polymerase chain reaction (PCR) at 3 polymorphic loci in the P53 gene, and analyzed with nonradioisotopic single-strand conformation polymorphism (Non-RI SSCP) analysis.


RESULTS
Out of 40 informative samples, LOH was detected in 13 samples, containing 4 of 7 in grade 3 (57%), 9 of 23 in grade 2 (39%), and none of 10 in grade 1 (10%). Statistical significance was observed between the LOH in grades 1 and 2, and in grades 1 and 3. An analysis of 5 cases showing malignant progression revealed that 3 (60%) showed an LOH in the primary tumor, and 2 showed LOH in recurrent tumors, in contrast to LOH found in 3 cases of 19 (16%) not showing malignant progression. Four cases with metachronous recurrence exhibited LOH; 2 at recurrent tumors, 1 only at the initial tumor, and 1 at both tumors.


CONCLUSIONS
The alterations of the P53 gene were considered to correlate with tumor grade, and contribute to the malignant progression of bladder cancer. LOH in the P53 gene may serve as a clinical indicator for prognosis in superficial bladder cancer.
Tsutsumi
M
M
Department of Urology, Kita-Ibaraki Municipal Hospital, Japan.
Sugano
K
K
Yamaguchi
K
K
Kakizoe
T
T
Akaza
H
H
D000483:Alleles; D018450:Disease Progression; D017353:Gene Deletion; D016158:Genes, p53; D006801:Humans; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000235:genetics; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014178:Translocation, Genetic; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology*