p53, p21, pRB, and p16 Expression Predict Clinical Outcome in Cystectomy With Bladder Cancer

Shariat, Shahrokh F.; Tokunaga, Hideo; Zhou, Jain; Kim, Ja Hong; Ayala, Gustavo; Benedict, William F.; Lerner, Seth P.

doi:10.1200/jco.2004.03.118

Cited by 292 publications

(264 citation statements)

References 22 publications

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“…In retrospective studies using tumour samples from radical cystectomy specimens, nuclear accumulation of p21 was detected in 64% of specimens and was an independent predictor of tumour recurrence and survival when concomitantly assessed with tumour grade, stage, lymph node status and p53 status. 22,26 P27 overexpression in human cells has been shown to result in cell cycle arrest in the G1 phase. In patients with muscleinvasive disease treated with radical cystectomy, p27 was the second most powerful cell cycle regulator after p53 for prediction of bladder cancer recurrence and survival.…”

Section: Biomarkers Of Prognosis and Therapeutic Efficacymentioning

confidence: 99%

“…Many studies support the association of p53 nuclear accumulation with tumour stage, lymphovascular invasion, lymph node metastasis, high-grade tumour, disease recurrence and bladder cancer specific death. [19][20][21][22][23][24][25] However, a metaanalysis by Malats that reviewed 117 studies spanning 10 years concluded that there is insufficient evidence to support that changes in p53 can be a marker of outcome in patients with bladder cancer. 32 A clinical trial investigated whether alterations of immunohistochemical p53 nuclear expression could prospectively identify patients that would benefit from the administration of adjuvant MVAC chemotherapy.…”

Section: Biomarkers Of Prognosis and Therapeutic Efficacymentioning

confidence: 99%

“…Biomarkers that enhance the predictive ability of standard clinicopathologic information and optimize prognostication are being discovered. [19][20][21][22][23][24][25][26][27][28][29][30] In addition, advanced technologies offer a systematic approach for identifying active targets for drug discovery and tailored therapeutics in bladder cancer. The method described here defines a "personalized selection" approach to advanced bladder cancer within this increasingly tailored diagnostic and therapeutic framework, since optimizing management of a patient's This review explores recent advances laying the groundwork toward making "personalized selection" a reality for patients with muscle invasive and metastatic bladder cancer.…”

Section: Introductionmentioning

confidence: 99%

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Personalized medicine in advanced urothelial cancer: when to treat, how to treat and who to treat

Ehdaie

Smith

Theodorescu

2013

CUAJ

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The past decade has provided an improved understanding of the molecular mechanism of bladder cancer by defining distinct pathways in tumorigenesis and progression. Advances in technologies, such as high-throughput transcript profiling, microarrays and proteomics, offer a systematic approach to identifying targets for bladder cancer diagnostics and drug discovery. This review presents a select outline of the advances in the development of biomarkers and targets for patient prognosis and therapy selection. This paper describes a representative cohort of recent studies that have the potential to significantly impact the management of muscle invasive and metastatic urothelial carcinoma of the bladder. Space constraints do not permit this review to be comprehensive and we apologize to the authors whose work we do not cite.

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Section: Biomarkers Of Prognosis and Therapeutic Efficacymentioning

confidence: 99%

Section: Biomarkers Of Prognosis and Therapeutic Efficacymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Personalized medicine in advanced urothelial cancer: when to treat, how to treat and who to treat

Ehdaie

Smith

Theodorescu

2013

CUAJ

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“…2 Bladder cancer has been shown to resist programmed cell death both with altered expression of pro-and antiapoptotic proteins. [3][4][5] Survivin is a member of the inhibitor of apoptosis (IAP) gene family that has been found to control mitotic progression and induces changes in gene expression that are associated with tumor cell invasiveness. 6,7 Survivin mRNA is selectively expressed during embryonic and fetal development, 8 becomes undetectable or expressed at low levels in most differentiated normal adult tissues, and is overexpressed in human cancers.…”

mentioning

confidence: 99%

Survivin expression is associated with bladder cancer presence, stage, progression, and mortality

Shariat

Ashfaq

Karakiewicz

et al. 2007

Cancer

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136

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BACKGROUNDThe purpose was to compare the differential expression of Survivin in normal bladder tissue, bladder transitional cell carcinoma (TCC) of different stages, and to determine whether expression of Survivin is associated with TCC clinical outcomes.METHODSImmunohistochemical staining for Survivin was carried out on archival bladder specimens from 9 normal controls and 222 consecutive patients who underwent radical cystectomy and bilateral lymphadenectomy. Lymph node tissue involved with TCC from 50 of the 222 cystectomy patients was also evaluated.RESULTSSurvivin was expressed in none of the normal bladder specimens, 64% of the cystectomy specimens, and 94% of the malignant lymph nodes. Multivariable analyses performed in the cystectomy patients revealed that Survivin expression was associated with disease recurrence (P = .040), disease‐specific mortality (P = .037), and all‐cause mortality (P = .044).CONCLUSIONSThe findings of the study provide a rationale for further evaluation of Survivin and its downstream signaling pathways in bladder cancer and raise the potential for Survivin‐targeted therapy for bladder cancer. Cancer 2007. © 2007 American Cancer Society.

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“…21 Alterations of the p53 and RB regulatory pathways are predominantly seen in clinically aggressive high-grade bladder cancer. [22][23][24][25][26][27][28] *P-values of Kaplan-Meier log-rank test.…”

Section: Discussionmentioning

confidence: 99%

Alterations in transcription clusters underlie development of bladder cancer along papillary and nonpapillary pathways

Kim

Tuziak

et al. 2005

Laboratory Investigation

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Bladder cancer develops in the urothelial lining from intraurothelial preneoplasia via two pathways, papillary and nonpapillary, which correspond to nonaggressive and aggressive forms of the disease. Because these two forms of cancer may develop via distinct molecular events, we examined the gene expression patterns in the development of bladder cancer from preneoplasia along papillary and nonpapillary pathways. The expression profiles of 19 pairs of RNA samples from adjacent urothelium and tumors were analyzed using cDNA microarrays. For selected genes their expressions were verified on a cohort of 251 bladder cancer patients using tissue microarray and immunohistochemistry and were related to clinicopathological parameters including follow-up data. We identified alterations in seven gene clusters controlling proliferation, differentiation, and programmed cell death that were common for papillary and nonpapillary cancer. In contrast, genes controlling cellular and stromal interactions were altered in the nonpapillary cancer. The expression levels of only two genes from this group could be used to define an aggressive form of the disease. Tumors characterized by the low expression of e-cadherin and the high expression of DNA a-topoisomerase II had a high propensity for distant metastasis and were associated with poor survival. Laboratory Investigation (2005) 85, 532-549. doi:10.1038/labinvest.3700250Keywords: cDNA microarray; bladder cancer; gene expression profile; tissue microarray; preneoplasia Many common human epithelial malignancies develop by progression of microscopically identifiable precursor conditions ranging from mild dysplasia to carcinoma in situ. 1 These conditions progress to clinically aggressive invasive cancer by multiple cumulative molecular events. 2 In fact, the earliest incipient changes occur in normal tissue even before preneoplastic lesions can be microscopically identified. The identification of abnormally expressed genes in such occult preneoplastic lesions may provide important clues as to the molecular pathways involved in the development of human cancer and facilitate early cancer detection and prevention.Carcinoma of the bladder is an exceptionally good candidate for such studies representing a model epithelial malignancy, which develops from microscopically recognizable intraurothelial preneoplastic lesions. [2][3][4] The fifth most frequent human cancer, it primarily affects people over the age of 50 years, and accounts for approximately 3% of all cancerrelated deaths. 5 The common bladder carcinomas arise via two distinct, but sometimes overlapping pathways, papillary and nonpapillary. 6-9 Approximately 80% of bladder tumors are superficially growing lesions that originate from urothelial hyperplasia. They frequently recur after excision but usually do not aggressively invade the bladder wall or metastasize. Most aggressive bladder cancers are of the solid, nonpapillary type and originate from intraurothelial precursor conditions such as dysplasia and carcinoma in situ. They a...

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p53, p21, pRB, and p16 Expression Predict Clinical Outcome in Cystectomy With Bladder Cancer

Abstract: Although altered expression of each of the four cell cycle regulators is associated with bladder cancer outcome in patients undergoing radical cystectomy, p53 is the strongest predictor, followed by p21, suggesting a more pivotal role of the p53/p21 pathway in bladder cancer progression.

Cited by 292 publications

References 22 publications

Personalized medicine in advanced urothelial cancer: when to treat, how to treat and who to treat

Personalized medicine in advanced urothelial cancer: when to treat, how to treat and who to treat

Survivin expression is associated with bladder cancer presence, stage, progression, and mortality

Alterations in transcription clusters underlie development of bladder cancer along papillary and nonpapillary pathways

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