Stains & CD markers
WT1

Editor-in-Chief: Debra L. Zynger, M.D.
Aliya N. Husain, M.D.

Minor changes: 18 June 2021

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PubMed Search: WT1[TI] pathology review

Aliya N. Husain, M.D.
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Cite this page: Nadeem U, Husain A. WT1. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/stainswt1.html. Accessed July 28th, 2021.
Definition / general
  • WT1 gene encodes for Wilms tumor protein located on chromosome 11p13
  • Expressed / mutated in several different tumors
Essential features
  • Interpretation is based on staining pattern and antibody used
    • Staining patterns: nuclear and cytoplasmic
    • Antibodies: against N and C terminal
  • Expressed in a broad spectrum of tumors, including malignant mesothelioma, ovarian epithelial tumors and sex cord stromal tumors, astrocytoma, glioblastoma, benign and malignant vascular tumors and desmoplastic malignant melanoma
  • Expression linked to poor prognosis of several tumors, including acute myeloid leukemia, pancreatic and colorectal cancers and astrocytoma and a better prognosis in high grade serous carcinoma of the ovary
  • Vaccination and immunotherapy directed against WT1 is in trials
Pathophysiology
  • Transcription factor essential for normal development of the urogenital system
  • Both tumor suppressing and tumorigenic role in several neoplasias, including breast, acute myeloid leukemia (AML) and mesothelioma
  • Affects genes of the Wnt / β-catenin pathway and p53 tumor suppressor pathway
Clinical features
  • WT1 mutations in Denys-Drash syndrome, diffuse mesangial sclerosis kidney, Fraiser syndrome, Wilms tumor in 15% of cases, congenital nephrotic syndrome, cytogenetically normal acute myeloid leukemia and prostate cancer (Adv Pediatr 2012;59:247)
  • Chromosomal translocation (11;22)(p13;q12) EWSR1-WT1 gene fusion in desmoplastic round blue cell tumor
  • Mutated in 1.45% of all carcinomas
Interpretation
  • Can be exclusively nuclear or cytoplasmic according to the antibodies used (anti-C or N terminus WT1 antibody)
  • Interpretation has to be based on the tissue being stained and the context
Uses by pathologists
  • Nuclear stain against N terminus (disregard any cytoplasmic staining in these tumors) to differentiate:
  • Cytoplasmic stain against N terminus to differentiate:
    • Benign and malignant vascular tumors (WT1+) from vascular malformations (WT1-) (J Am Acad Dermatol 2010;63:1052)
    • Mammary myofibroblastoma, epithelioid type (WT1+) from lobular breast lobular carcinoma (WT1-) (Acta Histochem 2014;116:905)
    • Young type fibromatosis, e.g. congenital / infantile fibrosarcoma, fibrous hamartoma of infancy, myofibroma / myofibromatosis and lipofibromatosis (WT1+) from adult type fibromatosis e.g. nodular fasciitis and desmoid type (WT1) (Acta Histochem 2014;116:1134)
  • Nuclear stain against C terminus to differentiate:
    • Desmoplastic round blue cell tumor (WT1+) from Ewing sarcoma / primitive neuroectodermal tumors, neuroblastomas or rhabdoid tumors of the kidney (WT1) (Am J Surg Pathol 2000;24:830)
Prognostic factors
  • Acute myeloid leukemias: WT1+ have mutations in exon 7 and 9 of WT1 genes, have a worse prognosis and are resistant to chemotherapy
  • Diffuse astrocytic tumors: WT1+ tumors have a higher WHO tumor grade, no IDH1 mutations and a poor outcome
  • Colorectal and pancreatic ductal adenocarcinoma: WT1+ have a poorer prognosis
  • High grade ovarian serous carcinomas: WT1+ have a better prognosis, especially when the tumor cells also express estrogen receptor (Gynecol Oncol 2016;140:494)
Microscopic (histologic) images

Contributed by Urooba Nadeem, M.D., Aliya N. Husain, M.D. and Jeffrey Schulte, M.D.

Pleura: malignant mesothelioma (H&E and WT1)

Omental mass: serous carcinoma (H&E and WT1)


Lymph node: metastatic Wilms (H&E and WT1)

Brain tumor: glioblastoma (H&E and WT1)

Skeletal muscle cytoplasmic, WT1

Positive staining - normal
Positive staining - disease
Negative staining
Molecular / cytogenetics description
Sample pathology report
  • Example:
    • This pleural tumor is immunoreactive for WT1, suggestive of an mesothelial versus a lung origin.
Additional references
Board review style question #1


    A 60 year old man presents with recurrent pleural effusions. A 2.3 cm solid mass is found on the CT scan. H&E sections are shown in the images. Which stain would be most compatible with the diagnosis?

  1. WT1-, calretinin-, cytokeretain AE1 / AE3+, TTF1+, BAP1 lost
  2. WT1+, calretinin+, cytokeretain AE1 / AE3+, TTF1-, BAP1 lost
  3. WT1+, calretinin+, cytokeratin AE1 / AE3+, TTF1+, BAP1 lost
  4. WT1-, calretinin-, cytokeratin AE1 / AE3-, TTF1-, BAP1 retained
Board review style answer #1
B. WT1+, calretinin+, cytokeretain AE1 / AE3+, TTF1-, BAP1 lost. The diagnosis is malignant mesothelioma. The best panel to separate malignant mesothelioma from an adenocarcinoma should include at least 2 mesothelial markers and 2 carcinoma markers. The most specific mesothelial markers are WT1 and calretinin. WT1 staining is nuclear in malignant mesothelioma. Cytokeratin is positive in both mesotheliomas and carcinomas; however, it is important to rule out malignancies from other cell lineages, e.g. melanoma and vascular tumors. BAP1 is mutated / lost in 55 - 66% of malignant mesotheliomas and this can be demonstrated by IHC.

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