Apoptotic and proliferation indexes in primary superficial bladder tumors

González‐Cámpora, Ricardo; Davalos-Casanova, Guillermo; Beato-Moreno, Antonio; Luque, Rafael J.; Alvarez-Kindelan, Jose; Requena, María J.; Montironi, Rodolfo; López-Beltrán, Antonio

doi:10.1016/j.canlet.2005.11.006

Cited by 16 publications

(5 citation statements)

References 26 publications

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“…Disease-specific death was any death because of bladder cancer in patients with documented metastatic or recurrent disease. Compared with the primary tumor, progression was defined in individual studies as development of a higher stage [ 6 , 14 ]; development of a higher stage and/or grade [ 27 , 31 ]; development of a higher stage and/or grade as well as development of regional or distant metastases [ 25 ]; development of a higher stage or metastasis [ 10 , 16 , 17 , 33 , 36 , 37 , 41 ], or development of a higher stage and muscle invasive cancer (≥ T2), distant metastasis, or death from bladder cancer [ 11 ]. Additional definitions of progression included development of MIBC (≥ T2) [ 34 , 45 , 47 ] and development of MIBC (≥ T2) and/or metastasis [ 15 , 49 , 50 ].…”

Section: Methodsmentioning

confidence: 99%

Significance of Ki-67 in non-muscle invasive bladder cancer patients: a systematic review and meta-analysis

Jeong

Kwak

et al. 2017

Oncotarget

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PurposeThis meta-analysis evaluated the prognostic significance of Ki-67 in non-muscle invasive bladder cancer (NMIBC).Materials and MethodsWe selected 39 articles including 5,229 patients from Embase, Scopus, and PubMed searches. The primary outcomes, recurrence-free survival (RFS), progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were determined using time-to event hazard ratios (HRs) with 95% confidence intervals (CIs). Study heterogeneity was tested by chi-square and I2 statistics. Heterogeneity sources were identified by subgroup meta-regression analysis.ResultsTwo studies were prospective; 37 were retrospective. Immunohistochemistry was performed in tissue microarrays or serial sections. A wide range of antibody dilutions and Ki-67 positivity thresholds were used. Study heterogeneity was attributed to analysis results in studies of RFS (p < 0.0001). Meta-regression analysis revealed that region and analysis results accounted for heterogeneity in PFS studies (p = 0.00471, p < 0.0001). High Ki-67 expression was associated with poor RFS (pooled HR, 1.78; 95% CI, 1.48–2.15), poor PFS (pooled HR, 1.28; 95% CI, 1.13–2.15), poor DSS (pooled HR, 2.24; 95% CI, 1.47–2.15), and worse OS (pooled HR, 2.29; 95% CI, 1.24–4.22).ConclusionsThe meta-analysis found that current evidence supports the prognostic value of Ki-67 in NMIBC patients.

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Section: Methodsmentioning

confidence: 99%

Significance of Ki-67 in non-muscle invasive bladder cancer patients: a systematic review and meta-analysis

Jeong

Kwak

et al. 2017

Oncotarget

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“…Although no mutations of DBC1 have been detected in bladder tumours, expression of DBC1 is silenced by promoter hypermethylation in bladder cancer cell lines, and it has been noticed that exogenous expression of DBC1 protein in human bladder tumour cell lines resulted in suppression of proliferation, and that DBC1‐mediated growth inhibition was due to an increase in the number of cells in the G 1 phase of the cell cycle, therefore suggesting a role for DBC1 in cell cycle control 21, 30, 31, 34–36. At present, prognostic information on DBC1 is limited in papillary urothelial tumours 37, 38.…”

Section: Introductionmentioning

confidence: 99%

Loss of heterozygosity at 9q32–33 (DBC1 locus) in primary non‐invasive papillary urothelial neoplasm of low malignant potential and low‐grade urothelial carcinoma of the bladder and their associated normal urothelium

López-Beltrán

Alvarez-Kindelan

Luque³

et al. 2008

The Journal of Pathology

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Tumour recurrence has a major impact on patients with non-invasive papillary urothelial tumours of the bladder. To explore the role of DBC1 (deleted in bladder cancer 1 locus), a candidate tumour suppressor gene located at 9q32-33, as prognostic marker we have performed loss of heterozygosity (LOH) testing in 49 patients with primary papillary urothelial tumours and associated normal urothelium. Data from the 38 tumours and 11 specimens of normal urothelium that were informative in the LOH study (D9S195 marker) showed that LOH in urothelium (45.4%) but not in non-invasive tumours (60.5%) was associated with tumour recurrence (p = 0.026) but not to grade or progression. Also, tumours whose normal urothelium had LOH were larger (p = 0.020) and showed cyclin D1 over-expression (p = 0.032). Non-significant increased expression of p53, p21Waf1, apoptotic index and tumour proliferation, and decreased expression of p27Kip1 or cyclin D3 also characterized tumours whose normal urothelium had LOH. The expression of these G1-S modulators, apoptotic index and tumour proliferation was more heterogeneous in papillary urothelial tumours, irrespective of having retained heterozygosity or LOH. Also, Bax expression decreased in papillary urothelial tumours having LOH (p = 0.0473), but Bcl-2 was unrelated to LOH status. In addition, FGFR3 protein expression decreased in LOH tumours (p = 0.036) and in those having LOH in their normal urothelium (p = 0.022). FGFR3 immunohistochemical expression was validated by western blot in selected cases. The survival analysis selected LOH in normal urothelium as a marker of disease-free survival (log-rank 5.32, p = 0.021), progression-free survival (log-rank 3.97, p = 0.046) and overall survival (log-rank 4.26, p = 0.038); LOH in tumours was significant in progression-free survival (log-rank 3.83, p = 0.042). It is concluded that LOH at the DBC1 locus in normal urothelium seems to be relevant in the prognosis of non-invasive papillary tumours of the bladder via selecting cases with increased proliferation, frequent alterations of the G1-S phase modulators, and decreased FGFR3 protein expression.

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“…Previous studies identified Ki-67 as an independent prognostic marker for recurrence, progression and disease-specific survival in noninvasive tumors ( table 2 ) [68][69][70][71][72][73][74][75][76][77][78] . Worth noting, however, are the varying cutoff values for positive immunostaining.…”

Section: Ki-67mentioning

confidence: 99%

Current Status of Prognostic Immunohistochemical Markers for Urothelial Bladder Cancer

Rosenblatt¹,

Jonmarker²,

Lewensohn³

et al. 2008

Tumor Biol

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The management and prognostication of patients with urothelial carcinomas (UCs), the most common histological type of bladder cancer, is mainly based on clinicopathological parameters. Several markers have been proposed to monitor this disease, including individual cell cycle-related proteins such as p53, pRb, p16, p21 and p27. Other putative markers are the oncogene products of FGFR3 and the ErbB family, proliferation markers including Ki-67, Aurora-A and survivin and different components within the immune system. In this review, a total of 12 parameters were evaluated and their discriminatory power compared. It is concluded that, in single-marker analyses, the proliferation markers Ki-67, survivin and Aurora-A offer the best potential to predict disease progression since they were all able to demonstrate independent prognostic power in repeated studies. Markers related to the immune system (e.g. CD8+ cells, regulatory T cells and cyclooxygenase-2 expression) or oncogene products of the ErbB family and FGFR3 are less powerful predictors of outcome or have not been equally well studied. The cell cycle-related proteins p53, pRb, p16, p21 and p27 have been extensively studied, but their usefulness as single prognostic markers remains unclear. However, in multimarker analyses, these markers appear to add prognostic information, indicating that they may contribute to more accurate treatment of UC.

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Apoptotic and proliferation indexes in primary superficial bladder tumors

Cited by 16 publications

References 26 publications

Significance of Ki-67 in non-muscle invasive bladder cancer patients: a systematic review and meta-analysis

Significance of Ki-67 in non-muscle invasive bladder cancer patients: a systematic review and meta-analysis

Loss of heterozygosity at 9q32–33 (DBC1 locus) in primary non‐invasive papillary urothelial neoplasm of low malignant potential and low‐grade urothelial carcinoma of the bladder and their associated normal urothelium

Current Status of Prognostic Immunohistochemical Markers for Urothelial Bladder Cancer

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