Genetic initiation, progression and prognostic markers in transitional cell carcinoma of the bladder: a summary of the structural and transcriptional changes, and the role of developmental genes

Adshead,; Kessling,

doi:10.1046/j.1464-410x.1998.00767.x

Cited by 21 publications

(13 citation statements)

References 106 publications

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“…Amplification of the gene encoding the D1 cyclin is seen in a variety of solid tumors, including breast adenocarcinoma, squamous cell carcinoma of head and neck, esophageal and bladder cancer (Ewen and Lamb, 2004). In bladder tumors, overexpression of the D1 cyclin protein is correlated with highdegree tumors and a short recurrence time but no association between tumor invasion or decreased survival and Cyclin D1 overexpression has been detected (Adshead et al, 1998).…”

Section: Main Amplified Genes In Human Neoplasiasmentioning

confidence: 99%

“…Amplification of the ERBB2 oncogene, regardless of protein overexpression, has frequently been detected in bladder tumors, although it has not yet been correlated with the development, progression and clinical course of the disease (Adshead et al, 1998;Brandau et al, 2001;Ohta et al, 2001). In these tumors as well as in breast tumors, amplification and overexpression of the c-erbB2/neu protein has been investigated with the purpose of possibly directing the treatment of positive patients towards the use of the monoclonal antibody Herceptin (trastuzumab), since the levels of gene amplification and protein expression are very similar to those found in patients with breast cancer (Ross and McKenna, 2001;Ross and Gray, 2003).…”

Section: Main Amplified Genes In Human Neoplasiasmentioning

confidence: 99%

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Gene amplification in carcinogenesis

2006

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Gene amplification increases the number of genes in a genome and can give rise to karyotype abnormalities called double minutes (DM) and homogeneously staining regions (HSR), both of which have been widely observed in human tumors but are also known to play a major role during embryonic development due to the fact that they are responsible for the programmed increase of gene expression. The etiology of gene amplification during carcinogenesis is not yet completely understood but can be considered a result of genetic instability. Gene amplification leads to an increase in protein expression and provides a selective advantage during cell growth. Oncogenes such as CCND1, c-MET, c-MYC, ERBB2, EGFR and MDM2 are amplified in human tumors and can be associated with increased expression of their respective proteins or not. In general, gene amplification is associated with more aggressive tumors, metastases, resistance to chemotherapy and a decrease in the period during which the patient stays free of the disease. This review discusses the major role of gene amplification in the progression of carcinomas, formation of genetic markers and as possible therapeutic targets for the development of drugs for the treatment of some types of tumors.

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Section: Main Amplified Genes In Human Neoplasiasmentioning

confidence: 99%

Section: Main Amplified Genes In Human Neoplasiasmentioning

confidence: 99%

Gene amplification in carcinogenesis

2006

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“…While Rb–negative bladder tumors are mostly muscle invasive, this is not the case in superficial bladder tumors. Some studies described a prognostic value of aberrant Rb expression and a statistical significant increased survival in patients with normal Rb expression [5, 10, 17]. …”

Section: Tumor Suppressor Genesmentioning

confidence: 99%

Bladder Cancer

Brandau

Böhle²

2001

European Urology

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“…2,[7][8][9] Therefore, many studies have been performed investigating new prognostic markers for the prediction of progression. [10][11][12] Nevertheless, there are still no accurate biomarkers available to predict progression in this large subgroup of patients.…”

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confidence: 99%

Stratification based on methylation of TBX2 and TBX3 into three molecular grades predicts progression in patients with pTa-bladder cancer

et al. 2015

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The potential risk of recurrence and progression in patients with non-muscle-invasive bladder cancer necessitates followup by cystoscopy. The risk of progression to muscle-invasive bladder cancer is estimated based on the European Organisation of Research and Treatment of Cancer score, a combination of several clinicopathological variables. However, pathological assessment is not objective and reproducibility is insufficient. The use of molecular markers could contribute to the estimation of tumor aggressiveness. We recently demonstrated that methylation of GATA2, TBX2, TBX3, and ZIC4 genes could predict progression in Ta tumors. In this study, we aimed to validate the markers in a large patient set using DNA from formalin-fixed and paraffin-embedded tissue. PALGA: the Dutch Pathology Registry was used for patient selection. We included 192 patients with pTaG1/2 bladder cancer of whom 77 experienced progression. Methylation analysis was performed and log-rank analysis was used to calculate the predictive value of each methylation marker for developing progression over time. This analysis showed better progression-free survival in patients with low methylation rates compared with the patients with high methylation rates for all markers (Po0.001) during a followup of ten-years. The combined predictive effect of the methylation markers was analyzed with the Coxregression method. In this analysis, TBX2, TBX3, and ZIC4 were independent predictors of progression. On the basis of methylation status of TBX2 and TBX3, patients were divided into three new molecular grade groups. Survival analysis showed that only 8% of patients in the low molecular grade group progressed within 5 years. This was 29 and 63% for the intermediate-and high-molecular grade groups. In conclusion, this new moleculargrade based on the combination of TBX2 and TBX3 methylation is an excellent marker for predicting progression to muscle-invasive bladder cancer in patients with primary pTaG1/2 bladder cancer.

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Genetic initiation, progression and prognostic markers in transitional cell carcinoma of the bladder: a summary of the structural and transcriptional changes, and the role of developmental genes

Cited by 21 publications

References 106 publications

Gene amplification in carcinogenesis

Gene amplification in carcinogenesis

Bladder Cancer

Stratification based on methylation of TBX2 and TBX3 into three molecular grades predicts progression in patients with pTa-bladder cancer

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