P53 Nuclear Overexpression and Disease Progression in Ta-Bladder Carcinoma

As, Sarkis; Zhang, Zuo‐Feng; Cordon‐Cardo, Carlos; Melamed, Jonathan; Dalbagni, Guido; Sheinfeld, Joel; Wr, Fair; Hw, Herr; Reuter, V E

doi:10.3892/ijo.3.2.355

Cited by 38 publications

(12 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Mutation frequencies of TP53 are higher in high grade and high stage tumours than in low grade superficial tumours, 24-26 57 and this is reflected in a clear association with outcome. [58][59][60][61][62] Several studies have documented a significant reduction in progression free interval for p53 positive tumours. Similarly, absence of the Rb protein, indicative of gene mutation, is found more frequently in tumours of high grade and stage and is clearly associated with poor outcome.…”

Section: Molecular Genetic Markers As Prognostic Indicators In Tccmentioning

confidence: 99%

What we could do now: molecular pathology of bladder cancer

Knowles

2001

Molecular Pathology

127

View full text Add to dashboard Cite

There is much information on the genetic alterations that contribute to the development of bladder cancer. Because it is hypothesised that the genotype of the cancer cell plays a major role in determining phenotype, this genetic information should impact on clinical practice. To date however, this has not happened. Some of the alterations identified in bladder cancer have clear associations with outcome-for example, mutational inactivation of the cell cycle regulator proteins p53 and the retinoblastoma protein (Rb). However, as single markers, these events have insuYcient predictive power to be applied in the management of individual patients. The use of panels of markers is a potential solution to this problem. Examples of suitable panels include those genes/ proteins with known impact on specific cell cycle checkpoints or with impact on cellular phenotypes, such as immortalisation, invasion, or metastasis. To evaluate such marker panels, large tumour series will be needed-for example, archival samples from completed clinical trials. The use of these valuable resources will require coordination of sample provision. This might involve central collection and distribution of tissue blocks, sections, or tissue arrays and the provision of patient follow up information to laboratories participating in a study. With the availability of microarray technologies, including cDNA and comparative genomic hybridisation arrays, the transcriptome and genome of transitional cell carcinomas of diVerent phenotypes can be compared and will undoubtedly provide a wealth of information with potential diagnostic and prognostic uses. Although these studies can be initiated using small local tissue collections, high quality collection of fresh tissues from new clinical trials will be crucial for proper evaluation of associations with clinical outcome. Funding for molecular pathological studies to date has been poor. To begin to translate molecular information from the laboratory to the clinic and to make maximum use of valuable urological patient resources in the UK, adequate funding and scientific energy are required. Whereas the latter is not in doubt, present funding for this type of translational research is inadequate. (J Clin Pathol: Mol Pathol 2001;54:215-221) Keywords: bladder cancer; molecular pathology A great deal of information has accumulated on the genetics of transitional cell carcinoma (TCC) in recent years. Numerous genes and genetic changes involved in tumour development have been identified and the literature abounds with papers that show clear associations of specific genetic changes or gene mutations with clinical parameters. Therefore, one might predict that this must have generated novel laboratory tests (for screening, diagnosis, prediction of prognosis, etc) or some prospective studies or clinical trials. However, not only is little of this information currently being applied in the clinical setting but also, on closer examination of the data, it is clear that additional information will be needed bef...

show abstract

Section: Molecular Genetic Markers As Prognostic Indicators In Tccmentioning

confidence: 99%

What we could do now: molecular pathology of bladder cancer

Knowles

2001

Molecular Pathology

127

View full text Add to dashboard Cite

show abstract

“…Analyzing the status of the p53 tumor suppressor oncoprotein, 36.3% of all TCC with a uniform urothelial differentiation showed a positive nuclear immunoreactivity (at least 10% positive cells), while others determinated p53 overexpression in a wide range of 22% to 78%, most probably reflecting different definitions of positivity [1,9,13,16,21,41,52,56,57,67]. Unlike most previous studies reporting expression of p53 at higher levels in high-grade and high-stage than in low-grade and low-stage carcinomas, we found such a correlation only for TCC with a papillary but not a solid pattern of growth.…”

Section: Immunohistochemical Findingsmentioning

confidence: 99%

Histogenesis of nonurothelial carcinomas of the urinary bladder from pre-existent transitional cell carcinomas. A histopathological and immunohistochemical study

Kunze

Francksen

2002

Urological Research

View full text Add to dashboard Cite

The histogenesis of nonurothelial carcinomas of the urinary bladder is difficult to understand, since the bladder is normally lined exclusively by transitional cell epithelium. To gain more insights into the pathogenesis of nonurothelial carcinomas, the morphology and immunohistochemistry of transitional cell carcinomas (TCC), mixed transitional cell and nonurothelial carcinomas, and pure nonurothelial carcinomas were comparatively studied. Of papillary and of nonpapillary (solid) TCC (overall incidence 6.8%), 4.8% and 15.4%, respectively, disclosed foci of altered celllular and architectural phenotypes, consisting of squamous epithelium, pseudoglandular formations, and true glands with or without mucus production. The diverse phenotypic variants develop obviously by a metaplastic process as a result of the well-known inherent potential of the urothelium to undergo several pathways of cellular differentiation. There is strong evidence that squamous cell carcinomas arise secondarily from a squamous metaplasia and adenocarcinomas from metaplastic glandular epithelium within pre-existing TCC following complete carcinogenic transformation of the initially bland-looking metaplastic tumor cells. The metaplastic origin of nonurothelial bladder carcinomas is supported by immunohistochemical findings. The high molecular weight cytokeratin 34betaE12 identifies tumor cells with squamous characteristics, helping to explain the development of squamous cell carcinomas. Secretion of MUC5AC apomucin is assumed to play a central role in the histogenesis of nonurachal mucus-producing adenocarcinomas, including signet ring cell carcinomas. Metaplastic phenotypic variants of TCC should be recognized as distinct tumor entities with the potential to transform into nonurothelial carcinomas and thus possibly implying a poorer clinical outcome than typical, uniform TCC.

show abstract

“…However, p53 overexpression by immunohistochemistry can occur without TP53 gene mutation and is associated with poor survival (54,55). Detection of the p53 protein by immunohistochemical staining is associated with poor prognosis, tumor progression, and/or increased risk of death from bladder cancer in patients with either superficial or locally advanced disease (56)(57)(58)(59)(60)(61)(62)(63). Other genes such as p21 (WAF1/CIP1) can modulate the prognosis of patients whose tumors exhibit altered p53 expression (64).…”

Section: Predicting the Development Of Invasive Diseasementioning

confidence: 99%

Use of Markers in Defining Urothelial Premalignant and Malignant Conditions

Schmitz‐Dräger

Fradet

et al. 2000

Scandinavian Journal of Urology and Nephrology

View full text Add to dashboard Cite

Markers have revealed the presence of phenotypically abnormal areas in histologically benign urothelium in bladders containing transitional cell carcinomas. This finding strongly suggests that at least some bladder cancers are associated with changes in the field and that markers can detect these lesions before they reach a grossly malignant stage. Markers have been used clinically for the detection of cancer in patients who are under regular surveillance for recurrence of bladder cancer. Much less information is available regarding the use of markers to detect bladder cancer without a prior history of the disease and for the prediction of which tumors are biologically more aggressive. However, ongoing clinical trials are addressing the latter issue. The type of specimen and its preparation will determine what type of markers can be analyzed. Although marker performance is based upon sensitivity and specificity, the prevalence of bladder cancer in the population being tested will dramatically affect the positive predictive value of an assay. Markers with high positive predictive value are indicators for interventions, such as biopsy, while markers with high negative specific values are useful for avoiding interventions. Cytology is used to detect occult high-grade neoplasms such as carcinoma in situ.While not yet clinically validated, tests with high negative predictive value could be used to decrease the frequency of cystoscopic evaluation. Markers must be validated by testing them prospectively using previously defined cut-off values. Furthermore, markers that will be used to alter treatment should be tested prospectively to determine the safety and cost-effectiveness of this strategy. Recommendations for future work include: (1) evaluation of markers in patients with dysplasia defined by the current pathologic classification; (2) evaluation of markers as indicators of tumor recurrence; (3) evaluation of markers as indicators of tumor progression; and (4) evaluation of markers in chemoprevention studies.

show abstract

P53 Nuclear Overexpression and Disease Progression in Ta-Bladder Carcinoma

Cited by 38 publications

References 0 publications

What we could do now: molecular pathology of bladder cancer

What we could do now: molecular pathology of bladder cancer

Histogenesis of nonurothelial carcinomas of the urinary bladder from pre-existent transitional cell carcinomas. A histopathological and immunohistochemical study

Use of Markers in Defining Urothelial Premalignant and Malignant Conditions

Contact Info

Product

Resources

About