Evaluation of overexpression of p53 tumor suppressor protein in superficial and invasive transitional cell bladder cancer: comparison with DNA ploidy.
OBJECTIVE
p53 tumor suppressor gene is considered to play a significant role in carcinogenesis. Mutations in the p53 are the most frequent genetic abnormalities encountered in human malignancies. Our aim was to investigate the expression of p53 oncoprotein in superficial and invasive transitional cell bladder cancer (TCC) as well as its correlation with established prognostic factors, such as histologic grade, tumor stage, DNA content, and survival.


METHODS
Forty-five patients with superficial TCC (Ta-T1) and 42 with invasive TCC (T2-T4) were included in our study. Material from transurethral biopsy was examined using an immunohistochemical method and the monoclonal antibody Pab 1801.


RESULTS
p53 tumor suppressor protein was overexpressed in 48.3% of TCC cases and more frequently in invasive than superficial TCCs (P = 0.03) and undetectable in the tumor adjacent to normal tissue. p53 positivity was related to the degree of differentiation and with the stage of the disease of invasive TCCs (P = 0.03 and P = 0.004, respectively), whereas no statistical significance was documented for superficial TCCs. Moreover, p53 overexpression demonstrated a statistical significance with DNA ploidy in superficial Ta-T1 tumors (P = 0.04) and was suggestive in invasive T2-T4 tumors (P = 0.08). There was no correlation of recurrence related to p53-positive superficial tumors (P = 0.29). Patients with p53-positive invasive TCCs showed statistically significant worse survival (P = 0.007), but in multivariate analysis, p53 positivity is not independently related to poor overall survival (P = 0.30). When we combined ploidy and p53 status, we realized that the subset of patients with aneuploidy and p53 positivity had the worst prognosis (P = 0.008).


CONCLUSIONS
The results suggest the involvement of p53 protein as a late event in bladder carcinogenesis. p53 does not seem to be a prognostic marker for recurrences of superficial tumors and is not independently related to survival. The aneuploidy of tumors correlates with the p53 positivity in bladder cancer. The combined expression of aneuploidy and p53 positivity in invasive tumors has strong association with the survival of patients.
Nakopoulou
L
L
Department of Pathology and Urology, Athens University Medical School, Greece.
Constantinides
C
C
Papandropoulos
J
J
Theodoropoulos
G
G
Tzonou
A
A
Giannopoulos
A
A
Zervas
A
A
Dimopoulos
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000782:Aneuploidy; D002295:Carcinoma, Transitional Cell / Q000737:chemistry* / Q000235:genetics / Q000401:mortality; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005500:Follow-Up Studies; D015870:Gene Expression; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D015996:Survival Rate; D016159:Tumor Suppressor Protein p53 / Q000032:analysis*; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000401:mortality
D004273:DNA, Neoplasm; D016159:Tumor Suppressor Protein p53