THE PREDICTIVE VALUE OF MUSCULARIS MUCOSAE INVASION AND p53 OVER EXPRESSION ON PROGRESSION OF STAGE T1 BLADDER CARCINOMA

Bernardini, S.; Billerey, C; Martin, Mickaël; Adessi, G. L.; Wallerand, Hervé; Bittard, Hugues

doi:10.1097/00005392-200101000-00011

Cited by 70 publications

(58 citation statements)

References 20 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.…”

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%

“…7 Some studies have shown that the overexpression of p53 and the loss of pRb expression are predictive of tumor recurrence, progression, or survival in patients with superficial transitional cell carcinoma of the urinary bladder. [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%

mentioning

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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“…Numerous studies have defined p53 overexpression in bladder cancer as nuclear immunostaining extent with a cutoff value of 20% [9,12,16,17]. Others have used various cutoff values to define overexpression, including 10% [13], 15% [19] or 35% [20 ](table 3). Most scoring systems are based on the extent and intensity of nuclear staining, which can be very subjective depending on the pathologists.…”

Section: Discussionmentioning

confidence: 99%

A Six-Week Course of Bacillus Calmette-Guérin Prophylaxis Is Insufficient to Prevent Tumor Recurrence in Nonmuscle Invasive Bladder Cancer with Strong-Positive Expression of p53

Choi

et al. 2010

Oncology

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Objective: To determine the impact of p53 overexpression on tumor recurrence after bacillus Calmette-Guérin (BCG) intravesical therapy in patients with nonmuscle invasive bladder cancer (NMIBC). Methods: Between January 1999 and December 2008, 275 patients who received six BCG intravesical instillations for NMIBC (transitional cell carcinoma) after transurethral resection were assessed for differences in outcomes according to the level of p53 overexpression. A multivariate logistic regression model was applied to assess the predictive capacity of variables for recurrence. Overexpression of p53 was determined using monoclonal p53-DO7 antibody. Results: In 275 subjects, the recurrence rate was higher based on the level of p53 expression (p = 0.019). Based on multivariate analysis, a strong-positive p53 >60% (p = 0.031) and tumor grade (p = 0.015) were significant predictors for recurrence. Patients with a strong-positive p53 >60% had a much lower 5-year biochemical recurrence-free survival rate than patients with p53 ≤60% (72.1 vs. 31.5%, p < 0.001). Conclusions: Strong overexpression of p53 was predictive of recurrence in patients with NMIBC undergoing intravesical BCG treatment. A 6-week induction course of BCG alone is not sufficient to prevent recurrence in patients with NMIBC with high p53 expression; additional prophylactic strategies are needed for these patients.

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“…16 Stage T 1 (lamina propria invasion) has been divided into T 1a (no muscularis mucosae invasion) and T 1b (muscularis mucosae invasion), which have a clinically significantly higher risk of progression. 17 Consequently, the tumors were dichotomized into superficial (T a -T 1a ) and invasive (T 1b and higher) groups as described previously. 18 DNA was extracted from individual bladder tumors and sediments of voided urine samples as described previously.…”

Section: Tumor Tissues and Voided Urine Samplesmentioning

confidence: 99%

Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia

Kim

Lee

Majewski

et al. 2006

Laboratory Investigation

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In this paper, we present whole-organ histologic and genetic mapping studies using hypervariable DNA markers on chromosome 13 and then integrate the recombination-and single-nucleotide polymorphic sites (SNPs)-based deletion maps with the annotated genome sequence. Using bladders resected from patients with invasive urothelial carcinoma, we studied allelic patterns of 40 microsatellite markers mapping to all regions of chromosome 13 and 79 SNPs located within the 13q14 region containing the RB1 gene. A whole-organ histologic and genetic mapping strategy was used to identify the evolution of allelic losses on chromosome 13 during the progression of bladder neoplasia. Markers mapping to chromosomal regions involved in clonal expansion of preneoplastic intraurothelial lesions were subsequently tested in 25 tumors and 21 voided urine samples of patients with bladder cancer. Four clusters of allelic losses mapping to distinct regions of chromosome 13 were identified. Markers mapping to the 13q14 region that is flanked by D13S263 and D13S276, which contains the RB1 gene, showed allelic losses associated with early clonal expansion of intraurothelial neoplasia. Such losses could be identified in approximately 32% bladder tumor tissue samples and 38% of voided urines from patients with bladder cancer. The integration of distribution patterns of clonal allelic losses revealed by the microsatellite markers with those obtained by genotyping of SNPs disclosed that the loss within an approximately 4-Mb segment centered around RB1 may represent an incipient event in bladder neoplasia. However, the inactivation of RB1 occurred later and was associated with the onset of severe dysplasia/ carcinoma in situ. Our studies provide evidence for the presence of critical alternative candidate genes mapping to the 13q14 region that are involved in clonal expansion of neoplasia within the bladder antecedent to the inactivation of the RB1 gene. Laboratory Investigation ( Keywords: SNP-based mapping; in situ neoplasia; alternative candidate genes near RB1; bladder in situ neoplasia; RB1 locus Recent studies provide evidence that many common epithelial cancers, including those arising in the bladder, begin as clonal in situ expansion of neoplastic cells, which show no or minimal deviation from the normal phenotype. 1-4 Such lesions often form plaques involving large areas of the affected mucosa and their expansion precedes the development of microscopically recognizable dysplasia or carcinoma in situ. 4,5 Identification of chromosomal regions associated with the initial expansion of neoplasia is a requisite for future identification of their positional candidate genes that may provide growth advantage for a neoplastic clone.

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THE PREDICTIVE VALUE OF MUSCULARIS MUCOSAE INVASION AND p53 OVER EXPRESSION ON PROGRESSION OF STAGE T1 BLADDER CARCINOMA

Abstract: In our study the depth of tumor invasion was a significant independent predictor of progression in patients with T1 bladder cancer. This result suggests that the depth of invasion in stage T1 should be included in the histopathological report.

Cited by 70 publications

References 20 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

A Six-Week Course of Bacillus Calmette-Guérin Prophylaxis Is Insufficient to Prevent Tumor Recurrence in Nonmuscle Invasive Bladder Cancer with Strong-Positive Expression of p53

Evidence for alternative candidate genes near RB1 involved in clonal expansion of in situ urothelial neoplasia

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