Topoisomerase IIα in Wilms’ tumour: gene alterations and immunoexpression

Tretiakova, Maria; Turkyilmaz, Muge; Grushko, Tatyana A.; Kocherginsky, Maria N.; Rubin, Charles M.; Teh, Bin Tean; Yang, Ximing J.

doi:10.1136/jcp.2005.031963

Cited by 22 publications

(16 citation statements)

References 22 publications

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“…On the other hand, in two microarray expression studies, TOPO-II was found to exhibit high expression in WT and was even suggested to be related to the chemosensitivity of the tumor 15,16 . In a recent publication, TOPO-II was likewise found to be overexpressed (but in anaplastic WT samples) and its increased expression correlated with WT tumor aggressiveness 17 . TOPO-II has been proposed as a diagnostic marker distinguishing mesoblastic nephromas from Wilms' tumors 15 .…”

Section: Discussionmentioning

confidence: 99%

Expression of Multidrug Resistance-Related Protein (Mrp-1), Lung Resistance-Related Protein (Lrp) and Topoisomerase-Ii (Topo-Ii) in Wilms' Tumor: Immunohistochemical Study Using Tma Methodology

Fridman¹,

Škarda²,

Pinthus³

et al. 2008

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Aims: MRP-1, LRP and TOPO-II are all associated with protection of the cells from the adverse eff ects of various chemotherapeutics. The aim of this study was to measure the expression of these proteins in Wilms' tumor (WT).Materials and Methods: TMA block was constructed from 14 samples of WT's and from xenografts derived from them. Sections of the TMA were used for immunostaining against MRP-1, LRP and TOPO-IIa.Results: All normal kidneys expressed MRP-1 but were either weakly or negatively stained for LRP and TOPO-IIa. In WT samples, MRP-1 was universally expressed, exclusively in the tubular component, while there was no expression of LRP and TOPO-IIa showed heterogeneous distribution. The xenografts varied in their MRP-1 and TOPO-IIa expression and exhibited weak/negative staining of LRP.Conclusions: This study shows that although all the proteins evaluated, had diff erent expression patterns in the tumor samples, the most prominent changes in expression were found for MRP-1. The exact clinical implications of these changes in expression and their relevance to the resistance of these tumors to chemotherapy requires further investigation. The fi nding of diff erent expression profi les for the multidrug resistance proteins in the original WT's and their xenografts suggests that the results of animal cancer models may be diffi cult to interpret.

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Section: Discussionmentioning

confidence: 99%

Expression of Multidrug Resistance-Related Protein (Mrp-1), Lung Resistance-Related Protein (Lrp) and Topoisomerase-Ii (Topo-Ii) in Wilms' Tumor: Immunohistochemical Study Using Tma Methodology

Fridman¹,

Škarda²,

Pinthus³

et al. 2008

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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“…TOP2A has been implicated as a marker of poor prognosis in numerous malignancies, including breast, renal cell, hepatocellular, prostate, and colorectal carcinomas [43,[45][46][47][48][49][50][51]. In addition, TOP2A has been reported to be a sensitive and specific marker for actively proliferating cells in colorectal carcinoma [44].…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical Validation of Overexpressed Genes Identified by Global Expression Microarrays in Adrenocortical Carcinoma Reveals Potential Predictive and Prognostic Biomarkers

Pang

Glover

et al. 2015

The Oncologist

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Background. Adrenocortical carcinoma (ACC) is a rare malignancy with a poor prognosis. The aim of this study was to identify novel protein signatures that would predict clinical outcomes in a large cohort of patients with ACC based on data from previous gene expression microarray studies. Materials and Methods. A tissue microarray was generated from the paraffin tissue blocks of 61 patients with clinical outcomes data. Selected protein biomarkers based on previous gene expression microarray profiling studies were selected, and immunohistochemistry staining was performed. Staining patterns were correlated with clinical outcomes, and a multivariate analysis was undertaken to identify potential biomarkers of prognosis. Results. Median overall survival was 45 months, with a 5-year overall survival rate of 44%. Median disease-free survival was 58 months, with a 5-year disease-free survival rate of 44%.The

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“…Microvessel densities were assessed as the vessel area normalized to total tissue area. Nuclear expression for FosB, c-Jun, and C/EBPh were quantified as the percentage of positive nuclei as previously described (22). Color-specific thresholds were used to determine brown (positive) and blue (negative) nuclei within the outlined areas of interest and to calculate the ratio of positively stained nuclei to all nuclei and expressed as a percentage (nuclear index).…”

Section: Methodsmentioning

confidence: 99%

Epidermal Growth Factor Receptor Controls Flat Dysplastic Aberrant Crypt Foci Development and Colon Cancer Progression in the Rat Azoxymethane Model

Dougherty

Sehdev

Cerda

et al. 2008

Clinical Cancer Research

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Purpose: Colonic carcinogenesis deranges growth-regulating epidermal growth factor receptors (EGFR). We previously showed that EGFR signals were up-regulated in human aberrant crypt foci (ACF), putative colon cancer precursors. The azoxymethane model of colon cancer recapitulates many aspects of human colonic tumors. Recent studies indicate that flat dysplastic ACF with increased h-catenin are tumor precursors in this model. We asked, therefore, if EGFR signals are required for flat dysplastic ACF development and cancer progression. Experimental Design: Rats received azoxymethane or saline, and standard chow or chow supplemented with gefitinib, an EGFR inhibitor, for 44 weeks. EGFR signals were quantified in normal colon, flat ACF, and tumors by computerized analysis of immunostains and Western blots. K-ras mutations were assessed by PCR and mRNA for egfr ligands by quantitative real-time PCR. Results: EGFR inhibition with gefitinib decreased the incidence of flat dysplastic ACF from 66% to 36% and tumors from 71% to 22% (P < 0.05). This inhibitor also reduced the overexpressions of cyclin D1 and Cox-2 in flat ACF. Furthermore, in flat ACF, EGFR blockade decreased the upregulation of c-Jun, FosB, phosphorylated active signal transducers and activators of transcription 3, and CCAAT/enhancer binding protein-h, potential regulators of cyclin D1 and Cox-2. In colonic tumors, EGFR blockade significantly decreased angiogenesis, proliferation, and progression while also increasing apoptosis (P < 0.05). Gefitinib also inhibited the activations of extracellular signal^regulated kinase, Src, and AKT pathways in tumors. Conclusions: We have shown for the first time that EGFR promotes the development of flat dysplastic ACF and the progression of malignant colonic tumors. Furthermore, we have mechanistically identified several transcription factors and their targets as EGFR effectors in colonic carcinogenesis.Colonic carcinogenesis is characterized by the accumulation of activating mutations in proto-oncogenes and inhibiting mutations in tumor suppressor genes. These mutations dysregulate pathways, including epidermal growth factor receptor (EGFR) signals that control cell growth, maturation, and cell death. Up-regulations of EGFRs and ligands have been described in many tumors, including colon cancers (1). Recently, we reported that EGFR signals were up-regulated in human aberrant crypt foci (ACF) identified in situ using image magnification chromoendoscopy (2). ACF are the earliest identifiable lesions in experimental colonic carcinogenesis and dysplastic ACF are believed to be precursors of colon cancer (3).EGFR (ErbB1) is a member of the ErbB family of receptor tyrosine kinases which also includes ErbB2, ErbB3, and ErbB4 (4). Ligand binding induces a conformational change, causing receptors to dimerize and activating the receptor's intrinsic tyrosine kinase. ErbB2 is unique in that it has no identified ligand, but is the preferred heterodimeric partner for other members. EGFR signals activate multiple pathways i...

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Topoisomerase IIα in Wilms’ tumour: gene alterations and immunoexpression

Cited by 22 publications

References 22 publications

Expression of Multidrug Resistance-Related Protein (Mrp-1), Lung Resistance-Related Protein (Lrp) and Topoisomerase-Ii (Topo-Ii) in Wilms' Tumor: Immunohistochemical Study Using Tma Methodology

Expression of Multidrug Resistance-Related Protein (Mrp-1), Lung Resistance-Related Protein (Lrp) and Topoisomerase-Ii (Topo-Ii) in Wilms' Tumor: Immunohistochemical Study Using Tma Methodology

Immunohistochemical Validation of Overexpressed Genes Identified by Global Expression Microarrays in Adrenocortical Carcinoma Reveals Potential Predictive and Prognostic Biomarkers

Epidermal Growth Factor Receptor Controls Flat Dysplastic Aberrant Crypt Foci Development and Colon Cancer Progression in the Rat Azoxymethane Model

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