Wilms' Tumor-1 (WT1, WT-1) Antibody Review

 

 

 

Introduction

  • a 52- to 54-kda transcription factor, is the gene product of Wilms' tumor 1 (wt1). PMID: 12914969

  • as a tumor suppressor gene involved in the development of Wilms' tumor. PMID: 7643450, PMID: 16547468

  • an IgG2a subclass monoclonal antibody, recognizes a human T lineage specific antigen (mol. wt 40,000). PMID: 6199141

  • WT1 gene encodes a zinc finger transcription factor involved in kidney and gonadal development and, when mutated, in the occurrence of kidney tumor and glomerular diseases. PMID: 16927106

  • originally identified as an inactivated gene in Wilms tumor, a childhood kidney cancer. PMID: 16698800

  • a reliable marker for the detection of the presence of leukemic cells. PMID: 16502587

  • Wt1(-KTS) as a novel transcriptional activator for the tissue-specific expression of the erythropoietin (EPO) gene. PMID: 16467207

  • a common marker of both hepatocyte and endothelial progenitors. PMID: 15607745

  • a reliable molecular marker of minimal residual disease. PMID: 15339675, PMID: 15179007, PMID: 12007019

  • a useful molecular marker for risk assessment in myelodysplastic syndromes (MDS) patients. PMID: 12743153

  • a tumor marker for leukemic blast cells. PMID: 10086730, PMID: 9669676

Normal Expression

  • two major WT1 isoforms occupy separate and dynamic intranuclear locations in which one isoform, WT1+KTS, preferentially associates with the nucleolus. PMID: 17109636

  • WT1 is expressed at elevated levels in most leukaemias, but it is also expressed at reduced levels in normal CD34+ haematopoietic stem cells and in progenitor cells of other tissues. PMID: 15528146

  • WT1 protein is normally expressed in the developing genitourinary tract, heart, spleen and adrenal glands and is crucial for their development. PMID: 14681305

  • In early embryos, WT1 protein was located in specific areas of the coelomic mesothelium adjacent to the nephric ducts, the myocardium or the primordia of the endodermal organs (gut, liver and lungs). These mesothelial areas also showed localized expression of Slug, a zinc-finger transcription factor involved in epithelial-mesenchymal transitions. WT1+ mesenchymal cells were always found below the immunoreactive mesothelial areas, either forming a narrow band on the surface of the endodermal organs (gut, liver and lungs) or migrating throughout the mesodermal organs (mesonephros, metanephros, gonads, spleen and heart). In the developing heart, the invasion of WTI+ cells started at stage HH26, and all the ventricular myocardium was pervaded by these cells, presumably derived from the epicardium, at HH30. PMID: 11291764

  • The Wilms' tumor suppressor gene ( WT1 ) was previously identified as being imprinted, with frequent maternal expression in human placentae and fetal brains. PMID: 9361029

  • WT1 was detected by immunohistochemistry in the normal mammary duct and lobule, and the patterns of expression were consistent with developmental regulation. PMID: 9223327

  • in fetal kidney, WT1 transcripts and protein are coordinately expressed, and strongly associated with differentiation of metanephric blastemal cells into epithelial cells. PMID: 7967503

  • WT1 protein was readily detectable in glomerular podocytes throughout adulthood. WT1 protein in Wilms' tumor was present in blastema and glomeruloid structures. Expression in the female gonad was linked to the different stages of granulosa cell development. In the male gonad, expression was restricted to Sertoli cells and their precursors, the embryonic tunica albuginea and the rete testis. The intracellular distribution of the WT1 protein was investigated by confocal laser microscopy and was demonstrated to be exclusively nuclear. PMID: 8306891

Abnormal Expression

  • Ninety-two percent of ovarian serous carcinomas and 80% of peritoneal serous carcinomas without serous carcinoma involving an endometrial polyp expressed WT-1. PMID: 16006803

  • WT-1 was uniformly positive in primitive undifferentiated stromal Wilms tumors (6 of 6) and negative in the differentiating and differentiated stromal elements of Wilms tumors (0 of 5). WT-1 was also negative in cellular mesoblastic nephromas (0 of 12), CCSKs (0 of 12), and synovial sarcomas (0 of 4). PMID: 15630525

  • Sixteen of 19 endometrial stromal neoplasms were positive with WT-1, most (14 of 16) with 4+ positivity. Staining was nuclear (5 cases), cytoplasmic (5 cases), or combined nuclear and cytoplasmic (6 cases). PMID: 15213600

  • The wild-type Wilms' tumor gene WT1 is overexpressed in human primary leukemia and in a wide variety of solid cancers. PMID: 16630117

  • WT1-positive tumors included tumor of the stomach, prostate, and biliary and urinary systems, and malignant melanomas. A majority of the positive cases showed diffuse or granular staining in the cytoplasm, whereas ovarian tumors and desmoplastic small round cell tumors frequently showed nuclear staining. Glioblastomas, some of soft tissue sarcomas, osteosarcomas, and malignant melanomas of the skin showed extremely strong cytoplasmic staining as compared with other tumors. PMID: 16547468

  • Wilms' tumor1 (WT1) protein is highly expressed in leukemic blast cells of myeloid and lymphoid origin. PMID: 16491848

  • WT1 protein is frequently detected in the cytoplasm of a subset of high-grade non-Hodgkin lymphomas (NHLs). PMID: 15894924  

  • -eight of 51 glioblastoma samples (94%) showed immunohistochemically positive staining of WT1 protein, whereas all 10 medulloblastomas examined were negative. PMID: 15696971

  • Wilms' tumor (WT1) gene is overexpressed in patients with most forms of acute leukemia. PMID: 15339675

  • The WT1 gene is considered to be highly expressed in patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia and chronic myeloid leukemia and is thought to play a key role in maintaining the viability of leukemia cells. PMID: 15182334

  • Overexpression of the WT1 gene was also demonstrated in 5/6 (83%) de novo small cell lung cancers by immunohistochemistry. PMID: 12115544

Expression Alteration

  • Wilms' tumor gene (wt1) is up-regulated in acute myeloid leukemia (AML) and a variety of leukemia cell lines. The expression of wt1 in these cells is proposed to have an anti-apoptotic effect. PMID: 16966277

  • Expression of WT1 is down-regulated in eutopic endometrium obtained during the midsecretory phase from patients with endometriosis. PMID: 16879825

Function

  • Our results establish a crucial role for WT-1 in early urogenital development. PMID: 8395349

  • WT1 gene expression in the proliferating colonies was highest on day 14, although less than in leukemia samples, confirming our hypothesis that WT1 gene is a surrogate marker of proliferation, not only in leukemogenesis but also, to a lesser degree, in normal cell proliferation. PMID: 16040384

  • WT1 protein expression is maintained during angiogenesis and malignant transformation of endothelial cells and can be considered as a new endothelial marker. PMID: 15982325

  • the wild-type WT1 gene is strongly overexpressed in beta-catenin mutant desmoid tumors and may play a role in tumorigenesis of desmoid tumors. PMID: 15540161

  • WT1 protein is a promising tumor antigen for cancer immunotherapy against leukemias and various kinds of solid tumors, including lung and breast cancer. PMID: 12215010

  • WT1 gene plays an essential role in the growth of solid tumors and performs an oncogenic rather than a tumor-suppressor gene function. PMID: 10189890

Diagnostic Value

  • WT-1 is useful in distinguishing ovarian serous carcinoma (OSC) (characteristically diffuse strong nuclear positivity) from uterine serous carcinoma (USC) (characteristically negative). PMID: 14764054

  • high levels of WT1 expression have been reported in patients with an unfavorable outcome in childhood acute leukemia. PMID: 16876863

  • WT1 seems to be associated with very poor survival of patients with osteogenic sarcoma metastasis. PMID: 16857797

  • expression of WT1 gene may be indicative of an unfavorable prognosis in patients with advanced serous epithelial ovarian carcinoma. PMID: 16606472

  • WT1 quantification is an informative molecular marker for minimal residual disease (MRD) in pediatric acute myeloid leukemia (AML) and is now performed as prospective analysis in ELAM02 protocol. PMID: 16575000

  • expression level of WT1 could be an additional marker to the standard parameters considered in risk assessment for multiple myeloma. PMID: 16471322

  • Wilms' tumor gene 1 (WT1) is overexpressed in the majority (70-90%) of acute leukemias and has been identified as an independent adverse prognostic factor, a convenient minimal residual disease (MRD) marker and potential therapeutic target in acute leukemia. PMID: 16341043

  • WT1 is a key molecule for tumour proliferation in a large number of human neoplasms most prominent in acute leukaemias, making it a suitable target for therapeutic strategies. PMID: 15920488

Review Articles

  • The many facets of the Wilms' tumour gene, WT1. PMID: 16987884

  • Cancer immunotherapy targeting WT1 protein. PMID: 12215010

  • The role of WT1 in oncogenesis: tumor suppressor or oncogene? PMID: 12215009

  • Regulation of gene expression by WT1 in development and tumorigenesis. PMID: 12215008

  • Wilms tumor gene (WT1) expression as a panleukemic marker. PMID: 12215007

  • A review of the Wilms' tumor 1 gene (WT1) and its role in hematopoiesis and leukemia. PMID: 12201948

  • WT1 as a novel target antigen for cancer immunotherapy. PMID: 12188920

  • WT1 proteins: functions in growth and differentiation. PMID: 11595161

  • The possible role and application of WT1 in human leukemia. PMID: 11372753

  • Wilms' tumor gene WT1: its oncogenic function and clinical application. PMID: 11372729

  • Wilms tumor and the WT1 gene. PMID: 11237525

  • WT1: what has the last decade told us? PMID: 10333728

  • Multiple roles for the Wilms' tumor suppressor, WT1. PMID: 10197591

  • The Wilms tumour gene WT1 in leukaemia. PMID: 9402320

  • The WT1 Wilms tumor gene product: a developmentally regulated transcription factor in the kidney that functions as a tumor suppressor. PMID: 8393820

  • WT1: a novel tumor suppressor gene inactivated in Wilms' tumor. PMID: 1313285

  • Role of the WT1 gene in Wilms' tumour. PMID: 1322241

Applications

 

Immunohistochemistry (IHC)

  • Archival, paraffin-embedded tissue from two patients with gonadoblastoma, one bilateral and both with concurrent germinomatous areas, were evaluated immunohistochemically with antibodies directed against I, MIS, WT1, and p53. PMID: 9388060

  • WT1 gene expression as a prognostic marker in advanced serous epithelial ovarian carcinoma: an immunohistochemical study. PMID: 16606472

  • In the present study, the expression of WT1 was examined in 494 cases of human cancers, including tumors of the gastrointestinal and pancreatobiliary system, urinary tract, male and female genital organs, breast, lung, brain, skin, soft tissues and bone by immunohistochemistry using polyclonal (C-19) and monoclonal (6F-H2) antibodies against WT1 protein. PMID: 16547468

  • WT1 expression was examined using immunohistochemistry applied on a tissue microarray of normal tissues and a panel of 100 EOC tissues. PMID: 16263157

  • The utility of calretinin, inhibin, and WT1 immunohistochemical staining in the differential diagnosis of ovarian tumors. PMID: 15754297

  • Immunohistochemical analysis showed that the WT1 protein was overexpressed in ESCC cells in 36 (95%) of the 38 examined. PMID: 15510596

  • The expression of the Wilms' tumor gene WT1 was examined by immunohistochemistry in 40 cases of pancreatic ductal adenocarcinoma. PMID: 15245594

  • We examined the expression of WT1 and p53 by immunohistochemistry in 69 cases of endometrial carcinoma (35 endometrioid, 18 clear cell, 16 serous), 68 cases of ovarian carcinoma (28 serous, 11 endometrioid, 18 clear cell, and 11 mucinous), 14 fallopian tube carcinomas (12 serous, 2 endometrioid), and 20 primary peritoneal serous carcinomas. PMID: 15084838

  • Immunohistochemical analysis of nuclear versus cytoplasmic staining of WT1 in malignant mesotheliomas and primary pulmonary adenocarcinomas. PMID: 11570906

  • WT1 staining reliably differentiates desmoplastic small round cell tumor from Ewing sarcoma/primitive neuroectodermal tumor. An immunohistochemical and molecular diagnostic study. PMID: 10989634

  • Immunohistochemical expression of WT1 by desmoplastic small round cell tumor: a comparative study with other small round cell tumors. PMID: 10843285

  • Immunohistochemical detection of the Wilms' tumor gene (WT1) in epithelial ovarian tumors. PMID: 10782413

  • Expression of the Wilms' tumour gene WT1 in the developing human and in paediatric renal tumours: an immunohistochemical study. PMID: 9292148

  • Immunohistochemical demonstration of Wilms tumour gene product WT1 in a canine "neuroepithelioma" providing evidence for its classification as an extrarenal nephroblastoma. PMID: 9147249

  • Immunohistochemical detection of the Wilms' tumour gene WT1 in desmoplastic small round cell tumour. PMID: 9147076

  • A sensitive immunohistochemical technique was established to localize the WT1 gene product in archival normal tissues and paediatric renal tumour samples. PMID: 8758208

Immunoprecipitation (IP)

  • Immunoprecipitation with an anti-WT1 monoclonal antibody showed that a 52- to 54-kd protein was present in 4 mesothelioma cell lines. PMID: 7856747

Tissue Microarray (TMA)

  • We studied the immunohistochemical expression of WT1 and p53 in 130 primary human endometrial carcinomas of various histological subtypes, grades, and stages using a tissue microarray. PMID: 15297187

  • Routine immunohistochemical staining for p53 and WT1 was performed in 70 endometrial carcinomas (39 endometrioid and 31 serous) of varying differentiation using tissue microarrays. PMID: 15084839

Western Blotting (WB)

  • Western blot analysis showed that WT1 protein was predominantly expressed in the cytoplasm of the tumor cells in two cases of lung adenocarcinoma, supporting the intracytoplasmic staining for WT1 using immunohistochemistry. PMID: 16547468

  • WT1 expression in six lymphoma/leukemia cell lines using Western blot methods after subcellular fractionation. PMID: 15894924

  • WT1 mRNA and protein expression was analyzed in a panel of human colon cancer cell lines and primary colon carcinomas by RT-PCR and Western blot analysis, respectively. PMID: 14961577

  • western blot analysis showed that between 10 and 50% of total cellular WT1 can be detected in the cytoplasm depending on the cell type. PMID: 14681305

  • A strong cytoplasmic staining was demonstrated in all RMS (11/11). The Western blot analysis confirmed the WT1 protein in the tissue, and the RT-PCR confirmed the presence of WT1 mRNA in the peripheral blood and tissue of one RMS patient. PMID: 12379755

  • we studied WT1 mRNA and protein in human endometrial extracts and in endometrial stromal cells (ESCs) differentiating into decidual cells in vitro, by RT-PCR and Western blotting, respectively. PMID: 11739471

  • Through size exclusion chromatography and Western blot analysis we determined the elution pattern of WT1. PMID: 10229205