p53 gene and protein status: the role of p53 alterations in predicting outcome in patients with bladder cancer.
OBJECTIVE
The p53 gene status (mutation) and protein alterations (nuclear accumulation detectable by immunohistochemistry; p53 protein status) are associated with bladder cancer progression. Substantial discordance is documented between the p53 protein and gene status, yet no studies have examined the relationship between the gene-protein status and clinical outcome. This study evaluated the clinical relationship of the p53 gene and protein statuses.


METHODS
The complete coding region of the p53 gene was queried using DNA from paraffin-embedded tissues and employing a p53 gene-sequencing chip. We compared p53 gene status, mutation site, and protein status with time to recurrence.


RESULTS
The p53 gene and protein statuses show significant concordance, yet 35% of cases showed discordance. Exon 5 mutations demonstrated a wild-type protein status in 18 of 22 samples. Both the p53 gene and protein statuses were significantly associated with stage and clinical outcome. Specific mutation sites were associated with clinical outcome; tumors with exon 5 mutations showed the same outcome as those with the wild-type gene. Combining the p53 gene and protein statuses stratifies patients into three distinct groups, based on recurrence-free intervals: patients showing the best outcome (wild-type gene and unaltered protein), an intermediate outcome (either a mutated gene or an altered protein) and the worst outcome (a mutated gene and an altered protein).


CONCLUSIONS
We show that evaluation of both the p53 gene and protein statuses provides information in assessing the clinical recurrence risk in bladder cancer and that the specific mutation site may be important in assessing recurrence risk. These findings may substantially impact the assessment of p53 alterations and the management of bladder cancer.
George
Ben
B
Department of Pathology, University of Southern California Keck School of Medicine, Los Angeles, CA 90033, USA.
Datar
Ram H
RH
Wu
Lin
L
Cai
Jie
J
Patten
Nancy
N
Beil
Stephen J
SJ
Groshen
Susan
S
Stein
John
J
Skinner
Donald
D
Jones
Peter A
PA
Cote
Richard J
RJ
D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D005091:Exons; D016158:Genes, p53; D006801:Humans; D009154:Mutation; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*
D014408:Biomarkers, Tumor; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53