WT1 expression in breast cancer disrupts the epithelial/mesenchymal balance of tumour cells and correlates with the metabolic response to docetaxel

Artibani, Mara; Sims, Andrew H.; Slight, Joan; Aitken, Stuart; Thornburn, Anna; Muir, Morwenna; Brunton, Valerie G.; Del-Pozo, Jorge; Morrison, Linda; Katz, Elad; Hastie, Nicholas D.; Hohenstein, Peter

doi:10.1038/srep45255

Cited by 38 publications

(34 citation statements)

References 63 publications

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“…Conflicting results are reported regarding WT1 expression and the prognosis of breast carcinoma. A study demonstrated that WT1 expression in breast cancer is correlated to poor prognosis, due to cancer-related epithelial-to-mesenchymal transition (EMT) and poor chemotherapy response [106]. Conversely, another study displayed that the immunoreactivity for WT1, together with RSPO1 and P16, was significantly associated with a more favorable disease-free survival [107].…”

Section: Wt1 Expression In Breast Carcinomamentioning

confidence: 99%

Immunohistochemical Expression of Wilms’ Tumor 1 Protein in Human Tissues: From Ontogenesis to Neoplastic Tissues

et al. 2019

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The human Wilms’ tumor gene (WT1) was originally isolated in a Wilms’ tumor of the kidney as a tumor suppressor gene. Numerous isoforms of WT1, by combination of alternative translational start sites, alternative RNA splicing and RNA editing, have been well documented. During human ontogenesis, according to the antibodies used, anti-C or N-terminus WT1 protein, nuclear expression can be frequently obtained in numerous tissues, including metanephric and mesonephric glomeruli, and mesothelial and sub-mesothelial cells, while cytoplasmic staining is usually found in developing smooth and skeletal cells, myocardium, glial cells, neuroblasts, adrenal cortical cells and the endothelial cells of blood vessels. WT1 has been originally described as a tumor suppressor gene in renal Wilms’ tumor, but more recent studies emphasized its potential oncogenic role in several neoplasia with a variable immunostaining pattern that can be exclusively nuclear, cytoplasmic or both, according to the antibodies used (anti-C or N-terminus WT1 protein). With the present review we focus on the immunohistochemical expression of WT1 in some tumors, emphasizing its potential diagnostic role and usefulness in differential diagnosis. In addition, we analyze the WT1 protein expression profile in human embryonal/fetal tissues in order to suggest a possible role in the development of organs and tissues and to establish whether expression in some tumors replicates that observed during the development of tissues from which these tumors arise.

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Section: Wt1 Expression In Breast Carcinomamentioning

confidence: 99%

Immunohistochemical Expression of Wilms’ Tumor 1 Protein in Human Tissues: From Ontogenesis to Neoplastic Tissues

et al. 2019

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“…22,25 However, the biological basis behind WT1 expression and poor clinical outcome is not well understood. 29 This may be due to inconsistencies in the published data regarding WT1 mRNA, 27,30 the protein expression levels in breast tumours 31,32 or the numerous WT1 isoforms that may have divergent functional roles 5,33 , 3,20 . Indeed, recent work suggests that the truncated WT1 transcript starting from intron 5 is tumour specific.…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, recent work suggests that the truncated WT1 transcript starting from intron 5 is tumour specific. 30 Furthermore, few studies have assessed WT1 expression in histopathological sub-types of breast carcinoma. This may be important as breast cancer is a profoundly heterogeneous disease whose correct classification is essential for optimal management.…”

Section: Introductionmentioning

confidence: 99%

WT1 expression in vessels varies with histopathological grade in tumour-bearing and control tissue from patients with breast cancer

et al. 2018

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Background The Wilms’ tumour protein (WT1), which influences tumour development and angiogenesis, is a promising therapeutic target in breast cancer. We hypothesised that WT1 expression would vary in endothelial cells in distinct sub-classifications of breast cancer. Methods WT1 expression and vascular density were quantified by immunohistochemical analysis of human ( n = 57) and murine breast cancers. Human tumours were sub-classified by histopathological grade, ER status and HER2 enrichment. Results WT1 was identified in endothelial (and epithelial and smooth muscle) cells in tumours and tumour-free tissues (controls) from patients and mice with breast cancer. WT1 expression was higher in tumours than in controls, but this was not due to increased endothelial WT1. Vascular WT1 in cancers decreased as histopathological grade increased. WT1 was higher in ER-positive versus ER-negative cancers. Strikingly, reduced WT1 expression in controls correlated with an increased Nottingham Prognostic Index score. Conclusions Expression of WT1 is increased in breast cancers but this is not limited to the vascular compartment. The association between reduced WT1 in tumour-free tissue and poor prognosis suggests a protective role for WT1 in the healthy breast.

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“…They suggested that WT1 may be a potential marker to predict survival in cancer patients. Another recent study suggested WT1 to play a role in the regulation of the epithelial‐mesenchymal balance of breast cancer cells . When comparing various tumor types, we could show that the specificity of the discrimination of these tumors depended strongly on the annotation of the area of interest.…”

Section: Discussionmentioning

confidence: 67%

MALDI Imaging for Proteomic Painting of Heterogeneous Tissue Structures

Kriegsmann¹,

Kriegsmann

Kriegsmann³

et al. 2018

Proteomics Clinical Apps

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Purpose To present matrix‐assisted laser desorption/ionization (MALDI) imaging as a powerful method to highlight various tissue compartments. Experimental design Formalin‐fixed paraffin‐embedded (FFPE) tissue of a uterine cervix, a pancreas, a duodenum, a teratoma, and a breast cancer tissue microarray (TMA) are analyzed by MALDI imaging and by immunohistochemistry (IHC). Peptide images are visualized and analyzed using FlexImaging and SCiLS Lab software. Different histological compartments are compared by hierarchical cluster analysis. Results MALDI imaging highlights tissue compartments comparable to IHC. In cervical tissue, normal epithelium can be discerned from intraepithelial neoplasia. In pancreatic and duodenal tissues, m/z signals from lymph follicles, vessels, duodenal mucosa, normal pancreas, and smooth muscle structures can be visualized. In teratoma, specific m/z signals to discriminate squamous epithelium, sebaceous glands, and soft tissue are detected. Additionally, tumor tissue can be discerned from the surrounding stroma in small tissue cores of TMAs. Proteomic data acquisition of complex tissue compartments in FFPE tissue requires less than 1 h with recent mass spectrometers. Conclusion and clinical relevance The simultaneous characterization of morphological and proteomic features in the same tissue section adds proteomic information for histopathological diagnostics, which relies at present on conventional hematoxylin and eosin staining, histochemical, IHC and molecular methods.

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WT1 expression in breast cancer disrupts the epithelial/mesenchymal balance of tumour cells and correlates with the metabolic response to docetaxel

Cited by 38 publications

References 63 publications

Immunohistochemical Expression of Wilms’ Tumor 1 Protein in Human Tissues: From Ontogenesis to Neoplastic Tissues

Immunohistochemical Expression of Wilms’ Tumor 1 Protein in Human Tissues: From Ontogenesis to Neoplastic Tissues

WT1 expression in vessels varies with histopathological grade in tumour-bearing and control tissue from patients with breast cancer

MALDI Imaging for Proteomic Painting of Heterogeneous Tissue Structures

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