Expression of cell-cycle regulatory proteins and their prognostic value in superficial low-grade urothelial cell carcinoma of the bladder

Santos, Lúcio Lara; Amaro, Teresina; Pereira, Sofia; Lameiras, Catarina; Lopes, Paula; Bento, Maria José; Oliveira, Jorge; Criado, Begoña; Lopes, Carlos

doi:10.1053/ejso.2002.1371

Cited by 50 publications

(37 citation statements)

References 38 publications

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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%

“…Some investigators have found that pRb immunoreactivity alone was not significantly associated with recurrence or progression in superficial bladder cancers. 18,20 However, other authors have reported that patients with abnormalities of both pRb and p53 expression in superficial bladder cancers had higher progression and lower survival rates than did those with normal expression of both genes, thus suggesting additive effects between the 2 genes. 15,16,20 Currently, there are very few reports on the predictive value of pRb immunoreactivity in relation to BCG therapy for superficial bladder transitional cell carcinomas (Table 4).…”

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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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

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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“…Specifically, recurrence was defined as the reappearance of a biopsy-proven lesion. Progression was defined as advancement in stage or dedifferentiation to grade 3 disease (Santos et al, 2003).…”

Section: Methodsmentioning

confidence: 99%

Prediction of progression in pTa and pT1 bladder carcinomas with p53, p16 and pRb

et al. 2004

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Currently available prognostic tools appear unable to adequately predict recurrence and progression in non muscle-invasive bladder carcinomas. We aimed to assess the prognostic value of immunohistochemical evaluation of the cell cycle markers p53, p16 and pRb. Paraffin blocks were obtained from 78 cases of pTa and pT1 transitional cell carcinomas, for which long-term follow-up was available. Representative sections were stained using antibodies against p53, p16 and pRb. Altered marker expression was found in 45, 17 and 30% of cases, respectively. Concurrent alteration of two or three markers occurred in 19% of cases, and was significantly associated with grade and stage. In univariate survival analysis, the concurrent alteration of any two markers was significantly associated with progression. The greatest risk was produced by alteration of both p53 and p16, which increased the risk of progression by 14.45 times (95% confidence interval (CI) 3.10 -67.35). After adjusting for grade and stage, this risk was 7.73 (CI 1.13 -52.70). The markers did not generally predict tumour recurrence, except in the 25 pT1 tumours. In these, p16 alteration was associated with a univariate risk of 2.83 (CI 1.01 -7.91), and concurrent p53 and p16 alteration with a risk of 9.29 (CI 1.24 -69.50). Overall, we conclude that the immunohistochemical evaluation of p53 and p16 may have independent prognostic value for disease progression, and may help guide management decisions in these tumours.

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Expression of cell cycle proteins in T1a and T1b urothelial bladder carcinoma and their value in predicting tumor progression

Mhawech

Greloz

Oppikofer

et al. 2004

Cancer

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The expression of cyclin D1 and p27 was associated with the most important prognostic factors (tumor stage and grade). The combination of p21 and p16 may have value in distinguishing T1b tumors from T1a tumors, although this finding must be evaluated in much larger series. Finally, none of the markers studied appeared to have predictive value for disease progression in patients with T1a and T1b urothelial bladder tumors.

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Expression of cell-cycle regulatory proteins and their prognostic value in superficial low-grade urothelial cell carcinoma of the bladder

Cited by 50 publications

References 38 publications

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

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

Prediction of progression in pTa and pT1 bladder carcinomas with p53, p16 and pRb

Expression of cell cycle proteins in T1a and T1b urothelial bladder carcinoma and their value in predicting tumor progression

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