Evaluation of p21 WAF1/CIP1 and cyclin D 1 expression in the progression of superficial bladder cancer

Liukkonen, Tapani; Lipponen, P; Raitanen, Mika; Kaasinen, Eero; Ala‐Opas, Martti; Rajala, Pertti; Kosma, V-M

doi:10.1007/s002400000116

Cited by 39 publications

(29 citation statements)

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“…Cyclin D1 expression in our study showed that lower expression is associated with poorly-differentiated tumours. This finding is consistent with the results of other studies [6,[8][9][10][11]14]. In addition, we found a lower expression in pT2-4 tumours compared with pTa and pT1 according to the findings of other investigators [6,8,11,14].…”

Section: Discussionsupporting

confidence: 83%

“…The relationship between cyclin D1 expression and the risk of subsequent recurrence is controversial. Some investigators found that the overexpression of cyclin D1 correlates with early recurrence in superficial bladder cancer [9,14]. On the other hand, Wagner et al [11] found that cyclin D1 positivity was not linked to the risk of recurrence or tumour progression, either in pTa or in pT1 carcinomas according to the results of our study.…”

Section: Discussionsupporting

confidence: 55%

“…Previous studies showed increased values of proliferative indices Ki-67 and PCNA to be correlated with recurrence rate and more aggressive behaviour of bladder cancer [49][50][51]. In our study we found an inverse relationship of cyclin D1 expression with the proliferative activity, as indicated by the findings of other investigators [8,14,52]. However, other studies found no correlation with proliferative activity as estimated with the Ki-67 score [10,11].…”

Section: Discussioncontrasting

confidence: 45%

“…As cut-off for the expression of cyclin D1, cyclin E, p21(Waf1/ Cip1) and p27(Kip1), those of 10 and 20% for cyclins and 5 and 20% for cyclins/CDK inhibitors were adopted for the study of recurrence and progression according to the other studies [11,14,18,19,28,30,31].…”

Section: Immunohistochemical Assessmentmentioning

confidence: 99%

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Expression Patterns of Cyclins D1, E and Cyclin-Dependent Kinase Inhibitors p21(Waf1/Cip1) and p27(Kip1) in Urothelial Carcinoma: Correlation with Other Cell-Cycle-Related Proteins (Rb, p53, Ki-67 and PCNA) and Clinicopathological Features

et al. 2004

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Introduction: The expression pattern of cyclins D1 and E, as well as cyclin-dependent kinase inhibitors p21(Wa1/Cip1) and p27(Kip1) and their relationship to tumour behaviour and patients’ prognosis was examined in 142 urothelial cell carcinomas. The expression of these proteins was also analyzed along with other cell-cycle-related proteins such as: p53, pRb and the proliferation-associated indices Ki-67 and proliferating cell nuclear antigen (PCNA). Patients and Methods: These molecule markers were localized immunochemically using the monoclonal antibodies anti-cyclin D1 (DCS-6), anti-cyclin E (13A3), anti-p21 (4D10), and anti-p27 (1B4) in 142 patients with urothelial cell carcinoma. Results: Focal positivity (<10% of tumour cells) or the absence of cyclin D1 immunostaining was observed in 105/142 (73.9%) of the tumours. Cyclin D1 expression was correlated with tumour grade and stage as well as with the existence of in situ component. In addition, cyclin D1 expression was positively correlated with p21(Waf1/Cip1) and p27(Kip1) and inversely with the Ki-67 score. Focal positivity (<20% of tumour cells) or the absence of cyclin E immunoreactivity was observed in 105/142 (73.9%) in all cases. Cyclin E expression was correlated with tumour stage. A positive relationship between cyclin E expression and the two associated proliferating indices Ki-67 and PCNA, as well as with p53 and p27(Kip1) proteins expression was noted. Absence or focal positivity (<5% of tumour cells) of p21(Waf1/Cip1) was detected in 88/142 (62%) of the carcinomas. p21(Waf1/Cip1) expression was correlated with tumour grade and stage. A positive relationship of its expression cyclin D1, cyclin E, p27 and pRb expression was observed. Absence or focal immunostaining (<20% of tumour cells) of p27 protein was detected in 55/141 (39%) in all cases. p27(Kip1) expression was correlated with tumour grade as well as with cyclins D1 and E. The prognostic significance of cyclins D1, E and cyclin-dependent kinase inhibitors p21(Waf1/Cip1), p27(Kip1) in determining the risk of recurrence and progression with both univariate (log rank test) and multivariate (Cox regression) methods of analysis showed no statistically significance differences. Conclusion: These findings suggest that the level of the cell cycle regulators studied does not seem to have a clinical value in terms of predicting the risk of early recurrence and progression. In addition the interrelationship probably means their contribution to the regulation of cell growth through different pathways in bladder carcinogenesis.

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Section: Discussionsupporting

confidence: 83%

Section: Discussionsupporting

confidence: 55%

Section: Discussioncontrasting

confidence: 45%

Section: Immunohistochemical Assessmentmentioning

confidence: 99%

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Expression Patterns of Cyclins D1, E and Cyclin-Dependent Kinase Inhibitors p21(Waf1/Cip1) and p27(Kip1) in Urothelial Carcinoma: Correlation with Other Cell-Cycle-Related Proteins (Rb, p53, Ki-67 and PCNA) and Clinicopathological Features

et al. 2004

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“…La mayoría de trabajos no la señalan como un factor predictivo independiente en tumores superficiales [24][25][26][27][28] , incluidos aquellos que consideran específicamente los tumores de alto riesgo y T1G3 3, 21 .…”

Section: Inmunohistoquímica De P21unclassified

Valor pronóstico de progresión de las moléculas reguladoras del ciclo celular en tumores vesicales T1G3

et al. 2005

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RESUMEN VALOR PRONÓSTICO DE PROGRESIÓN DE LAS MOLÉCULAS REGULADORAS DEL CICLOCELULAR EN TUMORES VESICALES T1G3 Introducción y Objetivos: El tumor vesical T1G3 constituye el grupo de tumores superficiales más agresivo. Nuevos factores pronósticos en el campo de la citogenética y la biología molecular han sido analizados, con resultados a menudo contradictorios, siendo escasos los trabajos específicos en tumores T1G3. Nuestro objetivo es determinar si en este grupo de tumores los marcadores inmunohistoquímicos presentan valor predictivo de progresión clínicamente útil, y por tanto con validez para indicar una actitud terapéutica precoz más idónea.Material y Métodos: Estudio retrospectivo de una serie de 83 pacientes afectos de tumor vesical T1G3, sobre los que analizamos un total de 14 variables; entre los nuevos factores predictivos: la determinación inmunohistoquímica de las proteínas reguladoras del ciclo celular: p53, p21 y bcl-2, así como la proteína Ki-67 como marcador de proliferación celular. Mediante análisis de regresión logística establecemos las variables pronósticas independientes para progresión tumoral.Resultados: El punto de corte establecido para Ki67 y p53 fue el 40% de células inmunomarcadas, 20% para p21 y 10% para Bcl-2. El análisis univariante puso de manifiesto diferentes tasas de progresión y tiempos libres de progresión en función de la inmunotinción de Ki67 y p53; sin embargo, la regresión logística demostró que solo la inmunohistoquímica de p53 presentaba valor predictivo independiente.Conclusiones: La determinación inmunohistoquímica de p53 presenta valor predictivo de progresión clínicamente útil en tumores vesicales T1G3, de manera que su determinación puede constituir un factor fundamental en las estrategias de tratamiento de estos tumores.Palabras clave: T1G3. Inmunohistoquímica. p53. ABSTRACT PROGNOSTIC VALUE FOR PROGRESSION OF THE REGULATING PROTEINS OF THE CELLULAR CYCLE IN PT1G3BLADDER TUMOURS Introduction and objective: Bladder tumor T1G3 constitutes the group of superficial tumors more aggressive. New prognostic factors in the field of the cytogenetics and molecular biology have been analyzed, with often contradictory results, being little the specific works in tumors T1G3. Our objective is to determine if in this group of tumors the immunohistochemical markers present predictive value of clinically useful progression, and therefore with validity to indicate more suitable a precocious therapeutic attitude Material and methods: Retrospective study of a series of 83 patients affected of bladder tumor T1G3, on which we analyzed a total of 14 variables; between the new predictive factors: the immunohistochemical determination of regulating proteins of the cellular cycle: p53, p21 and bcl-2, as well as the Ki-67 protein like marker of cellular proliferation. By means of logistic regression analisys we establish the independent prognostic variables for tumorlike progression.Results: The cut point established for Ki67 and p53 was 40% of inmmunomarked cells, 20% for p21 and 10% for Bc...

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Cyclin D3 expression in primary Ta/T1 bladder cancer

López-Beltrán¹,

Requena

Luque³

et al. 2006

J. Pathol.

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Cyclin D3 deregulation has recently been reported in bladder cancer but its prognostic significance remains uncertain. A cohort of 159 patients with stage Ta or T1 primary bladder tumours was investigated to determine the significance of cyclin D3 expression in association with other G1-S phase regulators of the cell cycle (p53, p21Waf1, p27kip1, cyclin D1), including tumour proliferation (ki67-MIB1); its association with conventional clinicopathological parameters; and the relationship between cyclin D3 and loss of heterozygosity (LOH) at the 9p21 (p16INK4a locus) chromosome region. The end point of the study was progression-free survival. Cyclin D3, other G1-S phase regulators, and tumour proliferation were investigated by immunohistochemistry and measured by the grid-counting method. To validate the immunohistochemical expression, cyclin D3 was additionally assessed by western blotting in selected cases. LOH at the 9p21 chromosome region (marker D9S171) was assessed in 125 cases using an AB Prism 310 genetic analyser and a set of microsatellite fluorescence-labelled primers. Cyclin D3 overexpression was related to larger tumour size (>5 cm; p < 0.0001) and high tumour proliferation (>10%; p = 0.025). Mean cyclin D3 expression increased with 2004 WHO grading categories in stage Ta (p = 0.035, ANOVA) and stage T1 (p = 0.047, t test) tumours. Cyclin D3 was not related to other clinicopathological parameters, G1-S phase modulators, or 9p21 LOH. Cox's multivariate analysis selected cyclin D3 as an independent predictor of progression-free survival (p = 0.0012, relative risk (RR) = 5.2366) together with tumour size (p = 0.0115, RR = 4.4442) and cyclin D1 (p = 0.0065, RR = 3.3023). Cyclin D3 expression had the highest risk ratio. Our results suggest that expression of cyclin D3 is relevant to the progression-free survival of patients with Ta/T1 bladder carcinomas.

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Evaluation of p21 WAF1/CIP1 and cyclin D 1 expression in the progression of superficial bladder cancer

Cited by 39 publications

References 0 publications

Expression Patterns of Cyclins D1, E and Cyclin-Dependent Kinase Inhibitors p21(Waf1/Cip1) and p27(Kip1) in Urothelial Carcinoma: Correlation with Other Cell-Cycle-Related Proteins (Rb, p53, Ki-67 and PCNA) and Clinicopathological Features

Expression Patterns of Cyclins D1, E and Cyclin-Dependent Kinase Inhibitors p21(Waf1/Cip1) and p27(Kip1) in Urothelial Carcinoma: Correlation with Other Cell-Cycle-Related Proteins (Rb, p53, Ki-67 and PCNA) and Clinicopathological Features

Valor pronóstico de progresión de las moléculas reguladoras del ciclo celular en tumores vesicales T1G3

Cyclin D3 expression in primary Ta/T1 bladder cancer

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