Improved objectivity of grading of TA,1 transitional cell carcinomas of the urinary bladder by quantitative nuclear and proliferation related features

Bol, M G W; Baak, Jan P. A.; Bruin, Peter C. de; Rep, Simon; Marx, Willem L.; Bos, Siebe D.; Kisman, O

doi:10.1136/jcp.54.11.854

Cited by 14 publications

(13 citation statements)

References 22 publications

(16 reference statements)

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“…Therefore, we have investigated cyclin D3 expression as a marker of progression‐free survival, its relationship with a subset of G1‐S modulators, tumour proliferation, and LOH at the 9p21 chromosome region ( p16INK4a locus); and its relationship with known conventional clinical and pathological variables. Indeed, it seems that aberrations of cell cycle regulators in different pathways are common in bladder tumours 9, 10, 19, 30–39. CDK inhibitors such as the downstream regulators p21Waf1 and p27kip1; cyclin D1 and cyclin D3, which are known upstream regulators; p53, a protein that plays a central role in cell cycle regulation; and tumour proliferation are frequently altered in bladder cancer and, therefore, the role of these aberrations in the prognosis of Ta/T1 bladder tumours needs to be substantiated.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

Cyclin D3 expression in primary Ta/T1 bladder cancer

López-Beltrán¹,

Requena

Luque³

et al. 2006

J. Pathol.

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“…A sample size of 300 fields of vision (FoV) with four points per FoV at 400Â magnification was used, which is a reliable and reproducible method [17]. HER-2 analyses were scored in WS by consensus scoring (by HS, EG, and IS), and according to the manufacturer's protocol.…”

Section: Scoring Protocols In Immunohistochemistrymentioning

confidence: 99%

Prognostic relevance of androgen receptor detection in operable breast cancer

Søiland

Kørner

Skaland

et al. 2008

Journal of Surgical Oncology

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“…But this is not an unexpected finding because it well known that the tumor proliferation index increases with grade in bladder tumors. 14,34,35 Our study suggests additional prognostic value for tumor size and the 2004 WHO grading scheme for noninvasive tumors: patients with PUNLMP or low-grade bladder carcinoma and tumors smaller than 3 cm have longer disease-free survival, a previously unreported finding in superficial bladder tumors classified according to the 2004 WHO grading scheme.…”

Section: Discussionmentioning

confidence: 69%

Prognostic Factors in Survival of Patients With Stage Ta and T1 Bladder Urothelial Tumors

López-Beltrán

Luque²,

Alvarez-Kindelan

et al. 2004

Am J Clin Pathol

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We studied 159 cases of superficial (stage Ta or T1) bladder tumors to determine the significance on survival of a subset of regulators of transition from G1 to S phase of the cell cycle (p53, p21Waf1, p27Kip1, cyclin D1, cyclin D3) and tumor proliferation (Ki-67 [MIB-1]). Clinical findings (patient age, sex, tumor size, grade, stage [Ta or T1]) were included in the analysis. Univariate analysis revealed association of tumor size (P = .0353), grade in stage Ta tumors (P = .0074), cyclin D1 expression (P = .0182), and Ki-67 index (P = .0033) with disease-free survival and of tumor size (P = .0005), stage (P = .0494), cyclin D3 expression (P = .0105), and Ki-67 index (P = .0272) with overall survival. Cox multivariate analysis revealed cyclin D1 expression and high proliferation index (disease-free) and tumor size, cyclin D3 expression, and high proliferation index (overall survival) as independent predictors. Results suggest that alterations of the progression from the G1 to S phase of the cell cycle are common in papillary urothelial bladder tumors. High tumor proliferation, expression of cyclins D1 and D3, and tumor size at diagnosis might be relevant predictors of survival in patients with stage Ta and T1 bladder urothelial tumors.

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Improved objectivity of grading of TA,1 transitional cell carcinomas of the urinary bladder by quantitative nuclear and proliferation related features

Cited by 14 publications

References 22 publications

Cyclin D3 expression in primary Ta/T1 bladder cancer

Cyclin D3 expression in primary Ta/T1 bladder cancer

Prognostic relevance of androgen receptor detection in operable breast cancer

Prognostic Factors in Survival of Patients With Stage Ta and T1 Bladder Urothelial Tumors

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