Prognostic Value of MIB-1 Score, p53, EGFr, Mitotic Index and Papillary Status in Primary Superficial (Stage pTa/T1) Bladder Cancer: A Prospective Comparative Study

Liukkonen, Tapani; Rajala, Pertti; Raitanen, Mika; Rintala, Erkki; Kaasinen, Eero; Lipponen, P

doi:10.1159/000020039

Cited by 85 publications

(47 citation statements)

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“…In this aspect, our results are consistent with those included in other multivariate studies, in terms of survival, 6,12,19,21 recurrence, 8,11,[15][16][17][18][19]25 and progression. [21][22][23]25 Our study shows that there are several significant variables in the prognosis of bladder TCC at T1 and T2a classifications. The expression of p53 shows its independence in predicting survival, progression, and metastasis development, whereas tumor multifocality, the T2a classification, and the presence of CIS in random bladder biopsy are the variables associated with a greater risk of recurrence.…”

Section: Discussionsupporting

confidence: 92%

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Multivariate analysis of survival, recurrence, progression and development of mestastasis in T1 and T2a transitional cell bladder carcinoma

Alonso

Pita-Fernández

González-Carreró

et al. 2002

Cancer

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BACKGROUNDDetermination of prognosis factors associated with survival, recurrence, progression, and development of metastasis in T1 and T2a transitional cell carcinoma (TCC) of the bladder is discussed.METHODSA study was conducted of a group of 210 patients with primary bladder TCC at classification T1 (n = 175) and T2aN0M0 (n = 35). A total of 177 variables were studied in each patient. The monoclonal antibodies used were the following: DO7 (p53) and MIB‐1 (Ki‐67). Prognosis was obtained using Kaplan–Meier methodology and Cox proportional hazards model.RESULTSThe average follow‐up period was 6.7 years. Cancer‐related survival rates at 5 and 10 years were 82.96% and 74.78%, respectively. The independent survival variables were the following: age and expression of p53. Recurrence free survival at 5 and 10 years stood at 51.80% and 42.71%, respectively. The independent recurrence variables were T2a classification, tumor multifocality, tumor size of greater than 3 cm, carcinoma in situ in random biopsy, and expression of Ki‐67. Progression free survival rates at 5 and 10 years were 75.31% and 69.16%, respectively. The independent progression variables were age, T2a classification, and expression of p53. Metastasis free survival rates at 5 and 10 years stood at 87.23% and 84.55%, respectively. The expression of p53 was the sole variable to provide an independent prediction of metastasis.CONCLUSIONSThe expression of p53 clearly has an independent effect on the prediction of survival, progression and development of metastasis, showing a dose–response effect. Tumor multifocality and T2a classification are the variables that best predict recurrence. Cancer 2002;94:1677–84. © 2002 American Cancer Society.DOI 10.1002/cncr.10376

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Section: Discussionsupporting

confidence: 92%

“…However, in the studies by Jahnson et al 6 and Liukkonen et al 21 the expression of p53 does not appear as an independent variable of survival.…”

Section: Discussionmentioning

confidence: 90%

Multivariate analysis of survival, recurrence, progression and development of mestastasis in T1 and T2a transitional cell bladder carcinoma

Alonso

Pita-Fernández

González-Carreró

et al. 2002

Cancer

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“…For example, the mutation and/or overexpression of epidermal growth factor receptor (43,44), erbB-2 receptor, hepatocyte growth factor and its receptor hepatocyte growth factor receptor/c-Met (45,46), and H-Ras (47-49) have been associated with bladder cancer and, in several reports, have been correlated with tumor aggressiveness. Other studies have demonstrated genetic alterations, including point mutations and gene deletions, which result in inactivation of the tumor suppressor genes such as p53 and Rb in bladder cancer (39,41,42).…”

Section: Discussionmentioning

confidence: 99%

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Boorjian¹,

Tickoo²,

Mongan³

et al. 2004

Clinical Cancer Research

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Purpose: Retinoids, which include vitamin A (retinol; ROL) and its derivatives, have been investigated in the treatment of bladder cancer. We have shown that expression of the enzyme lecithin:ROL acyltransferase (LRAT), which converts ROL to retinyl esters, is reduced in several human cancers. Here we evaluated expression of LRAT protein and mRNA in normal and malignant bladder tissue specimens from human patients. We also examined the effect of retinoids on LRAT expression in bladder cancer cell lines.Experimental Design: We evaluated 49 bladder cancer specimens for LRAT protein expression using immunohistochemistry with affinity-purified antibodies to human LRAT. LRAT mRNA expression was assessed using reverse transcription-PCR in bladder specimens from an additional 16 patients. We examined the effect of retinoic acid and ROL on LRAT mRNA expression in five human bladder cancer cell lines.Results: LRAT protein was detected throughout the nonneoplastic bladder epithelium in all of the specimens. In bladder tumors, LRAT protein expression was reduced compared with the nonneoplastic epithelium or was completely absent in 7 of 32 (21.9%) superficial tumors versus 16 of 17 (94.1%) invasive tumors (P < 0.001). All of the nonneoplastic bladder specimens tested (11 of 11) showed LRAT mRNA expression, compared with 5 of 8 (62%) superficial tumors and 0 of 5 (0%) invasive tumors (P ‫؍‬ 0.001). Three of five human bladder cancer cell lines expressed LRAT mRNA independent of retinoid exposure, whereas in two cell lines LRAT mRNA expression was induced by retinoid treatment.Conclusions: We report a significant reduction in LRAT expression in bladder cancer. Moreover, we demonstrate an inverse correlation of LRAT mRNA and protein expression with increasing tumor stage. These data suggest that loss of LRAT expression is associated with invasive bladder cancer.

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“…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%

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 MIB-1 Score, p53, EGFr, Mitotic Index and Papillary Status in Primary Superficial (Stage pTa/T1) Bladder Cancer: A Prospective Comparative Study

Cited by 85 publications

References 31 publications

Multivariate analysis of survival, recurrence, progression and development of mestastasis in T1 and T2a transitional cell bladder carcinoma

Multivariate analysis of survival, recurrence, progression and development of mestastasis in T1 and T2a transitional cell bladder carcinoma

Reduced Lecithin

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

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