Prognostic value of p53 nuclear accumulation and histopathologic features in T1 transitional cell carcinoma of the urinary bladder

Shariat, Shahrokh F.; Weizer, Alon Z.; Green, Aaran; Laucirica, Rodolfo; Frolov, Anna; Wheeler, Thomas M.; Lerner, Seth P.

doi:10.1016/s0090-4295(00)00756-1

Cited by 73 publications

(53 citation statements)

References 18 publications

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“…These results are consistent with the literature, 14,55,56 but since only 76 cases have been evaluated for DNA ploidy, we cannot exclude that our study may have lacked the power necessary to detect a significant result for this variable.…”

Section: Predictive Power Of Combined Cyclin D1 P27 Kip1 and Ki67 Indexsupporting

confidence: 92%

Cyclin D1 expression in papillary superficial bladder cancer: Its association with other cell cycle‐associated proteins, cell proliferation and clinical outcome

Sgambato

Migaldi

Faraglia

et al. 2001

Intl Journal of Cancer

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Cyclin D1 contributes to regulate G1 progression by forming a complex with different cyclin-dependent kinases. It has oncogenic properties and is frequently overexpressed in several human tumor types. In our study, expression of cyclin D1 and Ki67, a proliferation marker, was evaluated by immunohistochemistry in human papillary superficial (pTa-pT1) bladder cancers and was correlated with p27 Kip1 , p21 Waf1 and c-erbB-2 expression, with p53 gene status and protein expression, ploidy and cancer progression. Cyclin D1 expression was neither associated with tumor stage nor with tumor grade but high cyclin D1 expression (>25% positive nuclei) was significantly associated with p53 gene mutation (p ‫؍‬ 0.012), low p21 Waf1 (p ‫؍‬ 0.015) and high p27 Kip1 (p ‫؍‬ 0.016) protein expression. Ki67 expression was not associated with tumor stage but a high proliferation index (>10% positive nuclei) was significantly associated with high tumor grade (p ‫؍‬ 0.001) and with DNA aneuploidy (p ‫؍‬ 0.005). There was no significant difference in proliferative activity between high and low cyclin D1 expressor tumors. Patients whose tumors showed high expression of cyclin D1 displayed a significantly longer disease-free survival (p < 0.001 by log-rank test). Increased Ki67 expression was significantly associated with shorter disease-free survival (p ‫؍‬ 0.003). Both cyclin D1 (p ‫؍‬ 0.027; RR ‫؍‬ 1.898) and Ki67 (p ‫؍‬ 0.047; RR ‫؍‬ 1.932) protein expressions were independent predictors of reduced diseasefree survival on a multivariate analysis that also included p27 Kip1 expression and tumor stage. The simultaneous presence of low cyclin D1, low p27 Kip1 and high Ki67 expression defined a "high-risk" group of patients who displayed a significantly increased risk of recurrence (p < 0.0001). These results suggest that evaluation of cell cycle-associated markers can help to identify high-risk patients and may affect the management of patients with papillary superficial bladder cancer.

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Section: Predictive Power Of Combined Cyclin D1 P27 Kip1 and Ki67 Indexsupporting

confidence: 92%

Cyclin D1 expression in papillary superficial bladder cancer: Its association with other cell cycle‐associated proteins, cell proliferation and clinical outcome

Sgambato

Migaldi

Faraglia

et al. 2001

Intl Journal of Cancer

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“…Tumours superficial to the MM or reaching the MM but not passing through it were classified as pT1a, and tumours passing through the MM and invading the submucosa were considered to be pT1b [16,21,24]. A third proposal subclassifies T1 tumours as either with MM invasion (pT1b) or without (pT1a) [6,7,17,20,25,26]. The lack of uniformity between these systems of substaging could make data comparison difficult.…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Value of T1 Bladder Cancer Substaging: A Single Institution Retrospective Study

Soukup¹,

Dušková

Pešl³

et al. 2014

Urol Int

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Objective: To evaluate the prognostic value of the depth of lamina propria invasion in patients with T1 bladder cancer. Subjects and Methods: 200 patients were treated between the years 2002 and 2009. Tumours with depth of invasion above the muscularis mucosae level were categorised as pT1a and those with depth of invasion up to or beyond the muscularis mucosae as pT1b. Results: Categorisation for pT1a and pT1b was performed in 176 of 200 patients (88%). In 10 patients a muscle-invasive tumour was found in re-transurethral resection samples. 131 (79%) of 166 analysed patients had pT1a tumour and 35 (21%) had pT1b tumour. During the follow-up, in 101 (61%) patients the tumour had recurred and in 27 (16.3%) the tumour had progressed. Of all the investigated parameters, T1 substaging (p < 0.0001), grade (p = 0.0003) and the number of bacillus Calmette-Guérin instillations (p = 0.0490) were significant in predicting progression. The only significant factor for disease-specific survival was T1 substaging in univariable (p = 0.0008) and multivariable (hazard ratio 4.407) analysis. T1 substaging (p = 0.0149) and tumour multiplicity (p = 0.0448) have a statistically significant prognostic value with respect to overall survival. Conclusions: Deep invasion of the lamina propria is a significant adverse prognostic factor for tumour progression, disease-specific survival and overall survival.

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“…[8][9][10][11][12][13][14][15]20,21 However, other investigators have been unable to show that p53 overexpression is an independent predictor of either disease progression or patient survival (Table 4). [16][17][18][19] The prognostic value of nuclear p53 immunoreactivity in relation to BCG therapy for high-risk superficial bladder cancer is also debatable. Some studies have shown that p53 overexpression was possibly associated with high risk of progression, recurrence, and cancer death after BCG therapy [22][23][24] .…”

Section: Discussionmentioning

confidence: 99%

“…22 Yet, others have used 6%, 10%, 15%, or >20%, as a cutoff value to define overexpression ( Table 4). [8][9][11][12][13][14][15][16][17][18][19][20][21]24 The definition of pRb expression abnormality has also been arbitrary. In some studies, pRb expression abnormality has been defined as having an immunostaining extent of either 0% or >50%.…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10][11][12][13][14][15][16] Conversely, other investigators have found that these nuclear protein alterations were not independently prognostic for tumors. [16][17][18][19] There is, however, a scarcity of studies that report the prognostic predictive value of p53 and pRb status after bacille Calmette-Guerin (BCG) intravesical therapy for superficial bladder transitional cell carcinomas, and none after BCG plus interferon-alpha therapy.…”

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confidence: 99%

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Predictive value of p53 and pRb expression in superficial bladder cancer patients treated with BCG and interferon‐alpha

Esuvaranathan

Chiong

Thamboo

et al. 2007

Cancer

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BACKGROUNDNuclear p53 and retinoblastoma protein (pRb) were reported to be poor prognostic indicators for transitional cell carcinoma of the bladder. The authors sought to determine the prognostic value of nuclear p53 and pRb in superficial bladder transitional cell carcinoma patients who were treated with intravesical bacille Calmette‐Guerin (BCG) or BCG with interferon‐alpha (IFN‐α).METHODSA prospective histological review was performed for 80 superficial bladder transitional cell carcinoma patients who underwent postresection intravesical regimes of BCG (81mg, n = 33 or 27 mg, n = 20) or BCG (27 mg) with IFN‐α (n = 27), and followed for a mean of 4.5 years. Hematoxylin and eosin (H & E) and immunoperoxidase staining were performed on tissue sections. Nuclear p53 and pRb immunoreactivity were assessed semiquantitatively, by using a combination of staining extent and intensity, to categorize overexpression or underexpression. Data were analyzed by using chi‐square analysis, multiple logistic regression, and Kaplan‐Meier curves.RESULTSpRb expression was not associated with patient outcome after BCG‐alone therapy, but pRb underexpression was significantly associated with BCG nonresponse and tumor recurrence (P = .047) after BCG and IFN‐α (BCG + IFN‐α) therapy. Low‐grade tumors were associated with pRb overexpression, with or without nuclear p53 underexpression (P = .019; P = .043, respectively). p53 expression alone or in combination with pRb expression had no significant relation with tumor response to BCG alone or BCG + IFN‐α with respect to recurrence, progression, or cancer‐specific death.CONCLUSIONSNuclear pRb underexpression may be predictive of nonresponse and cancer recurrence after intravesical BCG + IFN‐α therapy. Nuclear p53 expression or its combination with pRb expression is not associated with post‐BCG clinical outcome, so p53 expression or p53 with pRb expression should not be used to influence decisions concerning BCG‐alone or BCG + IFN‐α therapy. Cancer 2007. © 2007 American Cancer Society.

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Prognostic value of p53 nuclear accumulation and histopathologic features in T1 transitional cell carcinoma of the urinary bladder

Cited by 73 publications

References 18 publications

Cyclin D1 expression in papillary superficial bladder cancer: Its association with other cell cycle‐associated proteins, cell proliferation and clinical outcome

Cyclin D1 expression in papillary superficial bladder cancer: Its association with other cell cycle‐associated proteins, cell proliferation and clinical outcome

The Prognostic Value of T1 Bladder Cancer Substaging: A Single Institution Retrospective Study

Predictive value of p53 and pRb expression in superficial bladder cancer patients treated with BCG and interferon‐alpha

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