p53 and RB Expression Predict Progression in T1 Bladder Cancer

Grossman, H. Barton; Liebert, Monica; Antelo, M.; Dinney, Colin P.N.; Hu, Shi Xue; Palmer, J. Lynn; Benedict, William F.

doi:10.1016/s0022-5347(01)62001-9

Cited by 43 publications

(61 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Rb is mutated or deleted in a wide array of human tumours, implying that it exerts its growth regulatory effects in a wide range of tissues. Recently, a number of groups have shown that alterations of both p53 and pRb have a cooperative negative effect in progression and survival in bladder cancer Grossman et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Cyclin D1 expression in transitional cell carcinoma of the bladder: correlation with p53, waf1, pRb and Ki67

et al. 2001

View full text Add to dashboard Cite

Summary Normal cell proliferation is closely regulated by proteins called cyclins. One of these, cyclin D1, in combination with its corresponding cyclin-dependent kinase (cdk), is essential for G 1 /S phase transition. Cyclin/cdk complexes are generally inhibited by cyclin-dependent kinase inhibitors(ckis), some of which are induced by wild-type p53. The aims of this study were: to investigate levels of cyclin D1 expression in transitional cell carcinoma (TCC) of the bladder; to correlate these results with data concerning the expression of p53, waf1, pRb and Ki67; and to determine whether cyclin D1 expression could predict clinical outcome. Paraffin-sections from 150 newly diagnosed bladder tumours (Ta/T1 = 97; T2-T4 = 53) were stained for cyclin D1 using immunohistochemistry and a cyclin D1 index assigned. These results were correlated with data relating to the expression of p53 and waf1 by the same tumours. A representative subset of 54 tumours (Ta/T1 = 28; T2-T4 = 26) was also stained for Ki67 and 55 were stained for pRb. The clinical course of each patient was recorded and multivariate analyses of risk factors for tumour recurrence, stage progression and overall survival were performed. Positive staining for cyclin D1 was found in 83% of tumours. The staining pattern varied between tumours with nuclear, cytoplasmic or a combination of the two evident in different tumours. 89% of Ta/T1 and 74% of T2-T4 tumours showed nuclear staining with or without cytoplasmic staining. The median value for cyclin D1 staining was significantly higher in Ta/T1 tumours (41%) compared with T2-T4 tumours (8%, P < 0.005) with 26% of muscle-invasive tumours demonstrating absent staining. In addition, the median value for cyclin D1 staining was significantly higher in G1/G2 tumours (43%) compared with G3 tumours (14%, P < 0.005). There was a significant positive correlation between expression of cyclin D1 and waf1 expression (P < 0.0001) as well as pRb expression but not between cyclin D1 expression and expression of p53. Ki67 expression was significantly associated with increasing tumour stage (P < 0.005) and histological grade (P < 0.05) but did not correlate with cyclin D1 expression. A cyclin D1 index ≥ 8% was associated with significantly better survival in those patients with muscle-invasive disease (T2-T4). In addition, there was a significantly higher progression rate for those patients with Ta/T1 disease whose tumours demonstrated cytoplasmic cyclin D1 staining. These results indicate that cyclin D1 expression is significantly higher in low-stage, well differentiated bladder tumours and strongly correlates with waf1 expression. In a multivariate analysis, cyclin D1 expression is an independent prognostic indicator of survival in those patients with muscle-invasive disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Cyclin D1 expression in transitional cell carcinoma of the bladder: correlation with p53, waf1, pRb and Ki67

et al. 2001

View full text Add to dashboard Cite

show abstract

“…6,21 Tumors were classified as p21-altered consisting of those tumors with no detectable or only very low levels of p21 nuclear immunoreactivity (0-9.9% of tumor cells showing p21 expression, p21 altered status) or p21 normal consisting of those tumors with moderate to high levels of p21 nuclear immunoreactivity (10% of tumor cells showing p21 expression). pRB immunoreactivity was assigned to one of three categories of nuclear staining in the tumor cells: no nuclear reactivity; normal heterogeneous; and strong homogeneous (more than 50%).…”

Section: Immunohistochemical Scoringmentioning

confidence: 99%

“…However, downstream pathways that contribute to urothelial transformation are not completely defined and are key factors too. 5,6 Members of the kinase inhibitor protein (KIP) family, p21 WAF1/CIP1 and p27 Kip1 are both p53-inducible and p53-independent cyclin-dependent kinase inhibitors that can arrest the cell by inhibiting DNA replication. Alteration of p53, pRB, p21 and p27 expression has prognostic significance in patients treated with radical cystectomy for bladder cancer.…”

mentioning

confidence: 99%

Cooperative effect of cell-cycle regulators expression on bladder cancer development and biologic aggressiveness

et al. 2007

View full text Add to dashboard Cite

The aim of this study was to evaluate the association between p53, p21, p27 and Rb expression, alone or in combination, with pathological features and clinical outcomes of urothelial carcinoma of the bladder. Immunohistochemical staining for p53, p21, p27 and pRB was performed on tissue microarrays comprising normal urothelium from nine controls, transurethral resection specimens from 74 patients with Ta, Tis and/or T1 bladder urothelial carcinoma, radical cystectomy specimens from 226 consecutive urothelial carcinoma patients, and lymph nodes with tumor invasion from 50 of the 226 cystectomy patients. All nine controls had normal status of biomarkers. The proportion of biomarkers alterations was highest in lymph node metastases. p53, pRB and p27 were associated with pathologic stage, lymphovascular invasion and lymph node metastases (P-valuesr0.050). Each biomarker alone, each combination of two biomarkers and the number of altered biomarkers were all independently associated with disease recurrence and bladder cancer-specific death (Pvaluesr0.046). In patients with organ-confined disease, p53, p21 and p27 were independently associated with disease recurrence and bladder cancer-specific death (P-valuesr0.046). There was a good but not perfect concordance in the expression of biomarkers between matched transurethral resection and cystectomy specimens (n ¼ 22; concordance rates: 77-86%) and between matched lymph node and cystectomy specimens (n ¼ 50, 70-92%). In conclusion, p53, p21, p27 and pRB have a cooperative/synergistic role in the biologic behavior of bladder urothelial carcinoma. In contrast to the use of single biological markers, evaluation of their combined status may improve prognostic models and help identify patients who might benefit from adjuvant therapies and in decision-making. Modern Pathology (2007) 20, 445-459.

show abstract

“…38 Additionally, since a phosphorylated pRb cannot bind E2F-1, hyperphosphorylated pRb, which can be identified immunohistochemically as intense nuclear staining, carries with it a similarly ominous prognosis as absence of Rb staining. 39,40 The p53 Tumor Suppressor Gene: The p53 gene encodes a 53kDa transcription factor with a critical role in DNA repair and apoptosis. Mutated p53 protein has a much longer half-life than wild-type p53, thus allowing its detection by immunohistochemistry.…”

Section: Retinoblastoma Tumor Suppressor Genementioning

confidence: 99%

Molecular Mechanisms and Pathways in Bladder Cancer Development and Progression

Jung

Messing

2000

Cancer Control

View full text Add to dashboard Cite

Background: The basis for bladder cancer development and progression is complex and involves genetic abnormalities. These abnormalities yield phenotypic changes that allow normal transitional cells to becomeity of these new cases, approximately 75%, are limited to the mucosa (stage Ta or Tis) and lamina propria (T1) at presentation, and most of these tumors can be removed by transurethral resection. Recurrence rates are high (30% to 85%), and 10% to 30% of "superficial" tumors (T1 or less) will subsequently progress to muscle invasive disease (stages T2-T4), which has a poorer prognosis. 2 For the remaining 25%, the initial presentation involves muscle invasive disease that will usually relapse with metastases (as well as localized disease persistence) within a median of 2 years if managed only by transurethral resection and intravesical therapy. 3 These data support the heterogeneous nature and malignant potential of transitional cell carcinoma

show abstract

p53 and RB Expression Predict Progression in T1 Bladder Cancer

Cited by 43 publications

References 31 publications

Cyclin D1 expression in transitional cell carcinoma of the bladder: correlation with p53, waf1, pRb and Ki67

Cyclin D1 expression in transitional cell carcinoma of the bladder: correlation with p53, waf1, pRb and Ki67

Cooperative effect of cell-cycle regulators expression on bladder cancer development and biologic aggressiveness

Molecular Mechanisms and Pathways in Bladder Cancer Development and Progression

Contact Info

Product

Resources

About