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

Leißner, Joachim; Hohenfellner, R.; Thüroff, Joachim W.; Koppen, Chris J. van; Wolf, Hans

doi:10.1159/000052482

Cited by 16 publications

(9 citation statements)

References 22 publications

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“…Although p21/WAF1 immunoreactivity alone was of no significant prognostic value and did not correlate with p53 positivity, there was a trend to a decreased tumor-free survival in patients with tumors that were positive for both p53 and p21/WAF1 compared to the remainder of the patients (p = 0.075). This is in agreement with our observation in pTa G2 bladder carcinomas and appears to indicate more aggressive tumors [30]. However, further studies are needed to elucidate the role of p21/WAF 1 in the carcinogenesis of bladder cancer.…”

Section: Discussionsupporting

confidence: 92%

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

Wolf¹,

Stober²,

Hohenfellner³

et al. 2001

Tumor Biol

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pT1 G3 bladder carcinomas are heterogeneous with respect to tumor recurrence and progression. Whereas some urologists treat these carcinomas by repeated transurethral resections often followed by intravesical chemotherapy or BCG instillation, others recommend cystectomy after tumor recurrence or early cystectomy after the initial diagnosis. Our goal was to determine the prognostic value of p53, p21/WAF1, Bcl-2, Bax, Bak, and Ki-67 immunoreactivity in these tumors. There were 30 patients with a new histopathological diagnosis of pT1 G3 urothelial carcinoma based on a transurethral resection specimen. Representative sections of these specimens were examined for the above markers. All patients were followed up regularly and were classified as being tumor free or having tumor recurrence or progression. The mean follow-up period was 43 months (range: 8–102 months). Twenty-five patients underwent radical cystectomy and 7 of these (28%) suffered from tumor progression and died of bladder cancer. In 5 patients, surgery was limited to a transurethral resection and 4 of these patients developed superficial tumor recurrence. There was a significant difference in tumor-free survival between patients with p53-immunoreactive (mean: 30 months) and p53-negative tumors (mean: 82 months; p = 0.0341). Bcl-2 positivity was also associated with decreased tumor-free survival (p = 0.043). The other markers had no significant prognostic impact. We conclude that p53 and Bcl-2 immunoreactivity labels the most aggressive pT1 G3 bladder carcinomas.

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Section: Discussionsupporting

confidence: 92%

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

Wolf¹,

Stober²,

Hohenfellner³

et al. 2001

Tumor Biol

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“…It has been suggested that p27 mediates G1 arrest induced by the transforming growth factor-ß, contact inhibition and serum deprivation epithelial cells, which indicates that normal level of p27 might be important in controlling cellular proliferation and opposing tumour progression [37]. Decreased or absent p27(Kip1) expression has been implicated as a powerful negative prognostic factor in a variety of malignancies including bladder cancer [17,20,34,35,38,39]. In addition, p21(Waf1/Cip1) and p27(Kip1) were considered as good markers for differentiation in human neoplasms [40][41][42].…”

Section: Introductionmentioning

confidence: 99%

Expression Patterns of Cyclins D1, E and Cyclin-Dependent Kinase Inhibitors p21(Waf1/Cip1) and p27(Kip1) in Urothelial Carcinoma: Correlation with Other Cell-Cycle-Related Proteins (Rb, p53, Ki-67 and PCNA) and Clinicopathological Features

et al. 2004

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Introduction: The expression pattern of cyclins D1 and E, as well as cyclin-dependent kinase inhibitors p21(Wa1/Cip1) and p27(Kip1) and their relationship to tumour behaviour and patients’ prognosis was examined in 142 urothelial cell carcinomas. The expression of these proteins was also analyzed along with other cell-cycle-related proteins such as: p53, pRb and the proliferation-associated indices Ki-67 and proliferating cell nuclear antigen (PCNA). Patients and Methods: These molecule markers were localized immunochemically using the monoclonal antibodies anti-cyclin D1 (DCS-6), anti-cyclin E (13A3), anti-p21 (4D10), and anti-p27 (1B4) in 142 patients with urothelial cell carcinoma. Results: Focal positivity (<10% of tumour cells) or the absence of cyclin D1 immunostaining was observed in 105/142 (73.9%) of the tumours. Cyclin D1 expression was correlated with tumour grade and stage as well as with the existence of in situ component. In addition, cyclin D1 expression was positively correlated with p21(Waf1/Cip1) and p27(Kip1) and inversely with the Ki-67 score. Focal positivity (<20% of tumour cells) or the absence of cyclin E immunoreactivity was observed in 105/142 (73.9%) in all cases. Cyclin E expression was correlated with tumour stage. A positive relationship between cyclin E expression and the two associated proliferating indices Ki-67 and PCNA, as well as with p53 and p27(Kip1) proteins expression was noted. Absence or focal positivity (<5% of tumour cells) of p21(Waf1/Cip1) was detected in 88/142 (62%) of the carcinomas. p21(Waf1/Cip1) expression was correlated with tumour grade and stage. A positive relationship of its expression cyclin D1, cyclin E, p27 and pRb expression was observed. Absence or focal immunostaining (<20% of tumour cells) of p27 protein was detected in 55/141 (39%) in all cases. p27(Kip1) expression was correlated with tumour grade as well as with cyclins D1 and E. The prognostic significance of cyclins D1, E and cyclin-dependent kinase inhibitors p21(Waf1/Cip1), p27(Kip1) in determining the risk of recurrence and progression with both univariate (log rank test) and multivariate (Cox regression) methods of analysis showed no statistically significance differences. Conclusion: These findings suggest that the level of the cell cycle regulators studied does not seem to have a clinical value in terms of predicting the risk of early recurrence and progression. In addition the interrelationship probably means their contribution to the regulation of cell growth through different pathways in bladder carcinogenesis.

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“…According to conventional references, [9][10][11][12][13][14][15] we thought that each positive rate in this study is proper. However, cocktail immunostaining in urine cytology smears was very highly sensitive, and it was suggested that the aberration of EGFR or p53 occurred in most bladder cancers.…”

Section: Discussionmentioning

confidence: 83%

Usefulness of Epidermal Growth Factor Receptor and p53 Cocktail Immunostaining for Differential Diagnosis with Urine Cytology

Ikeda

Funakoshi²,

Suzuki³

2009

Acta Cytologica

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

Cited by 16 publications

References 22 publications

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

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

Expression Patterns of Cyclins D1, E and Cyclin-Dependent Kinase Inhibitors p21(Waf1/Cip1) and p27(Kip1) in Urothelial Carcinoma: Correlation with Other Cell-Cycle-Related Proteins (Rb, p53, Ki-67 and PCNA) and Clinicopathological Features

Usefulness of Epidermal Growth Factor Receptor and p53 Cocktail Immunostaining for Differential Diagnosis with Urine Cytology

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