p53 expression compared with other prognostic factors in OMS grade-I stage-Ta transitional cell carcinoma of the bladder.
OBJECTIVE
Recent studies have investigated the possibility that p53 protein and some macroscopic tumoral features, such as diameter and focality of the lesion, play a significant prognostic role in bladder cancer progression. A retrospective study was conducted on papillary grade-I stage-Ta transitional cell carcinoma (TCC) of the bladder.


METHODS
p53 expression was evaluated using the immunohistochemical method. A group of 31 patients with papillary grade-I and stage-Ta TCC of the bladder with no recurrence or who recurred with no histological grading and staging variation in a 4-year mean follow-up period was compared with 28 grade-I and stage-Ta papillary TCC patients who underwent recurrences and a worsening in histological grading (grade II or grade III) or staging (T1) within the same period of time. The aim of this study was to investigate the hypothesis that altered patterns of expression of the protein products of the mutated p53 tumor-suppressor gene, when independently evaluated in comparison with other tumoral prognostic factors, are associated with tumor recurrence and progression in patients with Ta papillary grade-I TCC of the bladder.


RESULTS
Our data show that when a p53 threshold of > 0% was considered, 53.6% of patients with tumor progression in the follow-up period were p53-positive compared with only 16.1% of the nonprogressing group (chi 2 = 6, p = 0.02). On the contrary, p53 failed to show any value in predicting progression when a 5% threshold was considered (chi 2 = 1.12, p = 0.92). The multifocality of the tumoral lesion and recurrent tumor was highly predictive of tumor progression for both variables (chi 2 = 5.16, p = 0.003, and chi 2 = 0.23, p = 0.006, respectively). Multivariate analysis revealed p53 nuclear overexpression (at a threshold of > 0%) to be a single valuable prognostic factor of progression (OR = 10.20, p = 0.009) and recurrence (OR = 54.19, p = 0.01).


CONCLUSIONS
Our results lead to the conclusion that p53 immunohistochemical detection has no prognostic value in predicting tumoral relapse or progression of TaGI TCC of the bladder when a 5% positivity threshold is considered. On the contrary, when a p53 nuclear labelling of > 0% is considered as positive staining, this tumor marker becomes highly predictive of tumor recurrence and progression. These findings seem therefore to suggest the use of a slight p53 positivity (> 0%) as a valid tool in predicting the clinical behavior of TaGI bladder TCC. The prognostic impact of a multifocal lesion and a recurrent tumor as markers of progression is also confirmed by these results.
Casetta
G
G
Department of Urological Pathology, University of Turin, Italy.
Gontero
P
P
Russo
R
R
Pacchioni
D
D
Tizzani
A
A
D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000473:pathology* / Q000556:secondary; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis; D012189:Retrospective Studies; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*
D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53