The prognostic significance of apoptosis-associated proteins BCL-2, BAX and BCL-X in clinical nephroblastoma

Ghanem, Mazen A.; Kwast, Theo H. van der; Hollander, Jan C. den; Sudaryo, Mondastri Korib; Heuvel, Marry M. van den; Noordzij, Marinus A.; Nijman, Rien J.M.; Soliman, Emad; Steenbrugge, G.J. van

doi:10.1054/bjoc.2001.2146

Cited by 34 publications

(18 citation statements)

References 19 publications

(3 reference statements)

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“…In this study, mean immunoexpression of BCL-2 was different within the clinical evolution groups (healthy or relapse/fatal outcome). Besides, there was a higher BCL-2 expression in the healthy group, results not corroborated by the reviewed literature (13) . Moreover, its immunoexpression was higher in tumors with less than 550 g, which are also associated with favorable prognosis (35) .…”

Section: Discussioncontrasting

confidence: 58%

“…Krajewski et al (22) noted poor prognostic evolution in mammary carcinomas correlated with reduction of BAX immunoexpression. Germ cell tumors in children demonstrated correlation between the absence of BAX expression and poor prognosis (1) , whereas Wilms' tumor patients with higher staging showed reduction in BAX expression (13) . In this investigation, the highest positivity was detected in stage I when compared with other stages.…”

Section: Discussionmentioning

confidence: 96%

“…When programmed cellular death is impaired, the cell life span increases, which promotes neoplastic progression and radiotherapy/chemotherapy resistance (13) . Nevertheless, it is known that BCL-2 expression increases according to the differentiation rate of lesions.…”

Section: Discussionmentioning

confidence: 99%

“…Hence high BCL-2 expression rates may be present in well differentiated lesions, which would intrinsically have a better prognosis (2,26) . The immunoexpression of BCL-2 in the blastema component, which was assessed by Ghanem et al (13) in Wilms' tumor treated with preoperative chemotherapy, proved to be a useful tool in the correlation with clinical course. In this study, mean immunoexpression of BCL-2 was different within the clinical evolution groups (healthy or relapse/fatal outcome).…”

Section: Discussionmentioning

confidence: 99%

“…It is particularly worth mentioning those that are involved in cellular proliferation, apoptosis and angiogenesis, mainly p53. B-cell lymphoma 2 (BCK-2), BCL-2 associated protein X (BAX) and vascular endothelial growth factor receptor 1 (VEGFR1) (13,23,30) . In this study, we observed the immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 markers in 29 Wilms' tumors in order to propose new biomarkers applicable to diagnostic, prognostic and therapeutic approaches to this neoplasia.…”

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confidence: 99%

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Immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 proteins in nephroblastomas

Percicote¹,

Leme²,

Almeida³

et al. 2013

J. Bras. Patol. Med. Lab.

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Introduction: Nephroblastoma or Wilms' tumor is the most frequent renal cancer in children. Although its prognosis is favorable for most patients, it may relapse or have a fatal outcome. The characterization of risk groups by applying immunohistochemical biomarkers aims to adapt the treatment to its corresponding group as well as to reduce relapses and fatal outcome. p53, B-cell lymphoma 2 (BCL-2), BCL-2 associated protein X (BAX) and vascular endothelial growth factor receptor 1 (VEGFR1) are among the most widely studied biomarkers, which are related to the apoptotic pathway, DNA repair and neovascularization. Objective: The objective of this study is to assess the immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 in samples of human nephroblastoma and to correlate them with clinicopathological prognostic factors. Material and methods: Twenty-nine surgical specimens of nephroblastoma diagnosed from 1994 to 2007 were selected from the Anatomopathological Service of two hospitals in Curitiba. The immunohistochemical analysis of tissue microarrays was performed through immunoperoxidase staining and the yielded results were compared with clinicopathological prognostic factors. Results: The major immunohistochemical expression of VEGFR1 in blastema and epithelium presented positive association with the risk group. Hence this may be related to higher vascular neoplastic invasion apparently caused by the endothelial growth factor, which maximizes the chances of metastasis and ultimately changes tumor staging, risk group and clinical evolution. Conclusions: The immunohistochemical expression of VEGFR1 substantiated a directly proportional association with the nephroblastoma risk group.

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Section: Discussioncontrasting

confidence: 58%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 proteins in nephroblastomas

Percicote¹,

Leme²,

Almeida³

et al. 2013

J. Bras. Patol. Med. Lab.

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Prognostic classification of relapsing favorable histology Wilms tumor using cDNA microarray expression profiling and support vector machines

Williams

Hing

Greer

et al. 2004

Genes Chromosomes & Cancer

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Treatment of Wilms tumor has a high success rate, with some 85% of patients achieving long-term survival. However, late effects of treatment and management of relapse remain significant clinical problems. If accurate prognostic methods were available, effective risk-adapted therapies could be tailored to individual patients at diagnosis. Few molecular prognostic markers for Wilms tumor are currently defined, though previous studies have linked allele loss on 1p or 16q, genomic gain of 1q, and overexpression from 1q with an increased risk of relapse. To identify specific patterns of gene expression that are predictive of relapse, we used high-density (30 k) cDNA microarrays to analyze RNA samples from 27 favorable histology Wilms tumors taken from primary nephrectomies at the time of initial diagnosis. Thirteen of these tumors relapsed within 2 years. Genes differentially expressed between the relapsing and nonrelapsing tumor classes were identified by statistical scoring (t test). These genes encode proteins with diverse molecular functions, including transcription factors, developmental regulators, apoptotic factors, and signaling molecules. Use of a support vector machine classifier, feature selection, and test evaluation using cross-validation led to identification of a generalizable expression signature, a small subset of genes whose expression potentially can be used to predict tumor outcome in new samples. Similar methods were used to identify genes that are differentially expressed between tumors with and without genomic 1q gain. This set of discriminators was highly enriched in genes on 1q, indicating close agreement between data obtained from expression profiling with data from genomic copy number analyses.

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Molecular Targeted Therapy for Wilms’ Tumor

Geller¹,

Dome

2010

Molecularly Targeted Therapy for Childhood Cancer

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The prognostic significance of apoptosis-associated proteins BCL-2, BAX and BCL-X in clinical nephroblastoma

Cited by 34 publications

References 19 publications

Immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 proteins in nephroblastomas

Immunohistochemical expression of p53, BCL-2, BAX and VEGFR1 proteins in nephroblastomas

Prognostic classification of relapsing favorable histology Wilms tumor using cDNA microarray expression profiling and support vector machines

Molecular Targeted Therapy for Wilms’ Tumor

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