PCNA and p53 in Urinary Bladder Cancer: Correlation with Histological Findings and Prognosis

Abstract

Background: This study aimed to immunohistochemically examine the expression of proliferating cell nuclear antigens (PCNA) and p53 protein in transitional cell carcinomas (TCC) of the urinary bladder, and to investigate possible correlations of this expression with the tumor grade or stage, tumor recurrence, and prognosis of the disease. Materials and Methods:The immunohistochemical status of the PCNA and p53 proteins were determined on paraffin-embedded sections from 128 patients with TCC of the urinary bladder, using PC-10 and D O 7 as the primary antibodies. Positive staining were represented by scores (Labeling Index; LI, %) calculated as the percent of positive cells among all neoplastic cells counted. The findings were compared to the patients' histopathological features. Patients who underwent transurethral resection were divided into groups with "low" and "high" scores for PCNA and p53, respectively, and the tumor recurrence rate was compared among the groups. Patients who underwent total cystectomy were similarly divided into "low" and "high" score groups, and survival rates of the groups were compared. Results: PCNA expression was observed in 66 of 128 patients (51.6%), with a mean labeling index of 26.6%. Overexpression of p53 was observed in 65 of 128 patients (50.8%), with a mean labeling index of 35.3%. There were significant correlations of the PCNA and p53 indices with both histological grade and stage of the tumor. In the TUR group, there were no statistically significant differences in recurrence rate between the groups with high or low scores for either PCNA or p53. In the total cystectomy group, there was a significant correlation between survival rate and positive staining for PCNA, but not for p53. The relationship between 2 parameters, PCNA and p53 scores, was not significant (linear correlation coefficient, r = 0.67). Conclusions: PCNA and p53 status in transitional cell carcinomas of the urinary bladder is related to the histopathological findings. We also suggest that immunohistochemical staining for PCNA provides significant clinical information which may be useful in the initial selection of therapy. However, overexpression of p53 does not appear to represent an independent prognostic marker in bladder tumors.

Prognostic Significance of Histopathological Grading and Immunoreactivity for p53 and p21/WAF1 in Grade 2 pTa Transitional Cell Carcinoma of the Urinary Bladder

“…Literature data on the prognostic value of p53 immunoreactivity are controversial [5, 6, 7]. However, in contrast to previously published data, this is one of the few series in which the prognostic relevance of p53 immunohistochemistry was evaluated in a very homogeneous group of patients.…”

“…A number of retrospective studies has shown a correlation between p53 immunoreactivity and tumour grade and stage, which may be of prognostic relevance in superficial bladder cancer. However, the clinical data as to the significance of p53 as a prognostic indicator are controversial [5, 6, 7]. …”

p53 Expression Predicts Progression and Poor Survival in T1 Bladder Tumours

“…High levels of p53 protein have been associated with high grade [35], high–stage tumours [36], cell proliferation [12, 13]and poor survival [12]in TCC of the bladder. The role of p53 protein in progression of superficial bladder cancer has been studied recently by different authors [10, 11, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29]with conflicting results: whereas some authors observed that p53 expression studied by immunohistochemistry was an independent prognostic marker for bladder cancer [11, 14, 16, 19, 20, 27, 28], others found that p53 was not of prognostic importance or that it was not independent of other markers [10, 15, 17, 18, 21, 22, 23, 24, 25, 26, 29]. Most of these studies used a small number of superficial bladder cancer patients and they evaluated both Ta and T1 tumours.…”

“…p53 overexpression has been proven to be related to high stage [10, 11], rapid proliferation [12, 13]and poor survival [11]. Nevertheless, controversial results on the role of p53 in tumour progression of superficial bladder neoplasms have been reported in the literature [10, 11, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29]. …”

Prognostic Value of p53, p21/WAF1, Bcl-2, Bax, Bak and Ki-67 Immunoreactivity in pT1 G3 Urothelial Bladder Carcinomas

“…Therefore, a decreased p21/WAF1 expression leads to a suppression of the G1-S checkpoint with a decreased time for DNA repair and increases in mutations during DNA replication [9][10][11]. Thus, p21/WAF1 expression may reflect the functional status of p53 [12]. Because p21/WAF1 is induced by p53, a lack of p21/WAF1 expression may help to detect those patients who do not develop tumor progression or recurrence despite a p53 mutation.…”