WT-1 (Wilms’ tumour 1)

WT-1 (Wilms’ tumour 1) is a type of protein called a transcription factor. It was originally identified due to its association with Wilms’ tumour, a type of kidney cancer that affects children. It plays a critical role in the development and function of the kidneys and testis, influencing gene expression related to cellular growth and differentiation. Pathologists use WT-1 as a diagnostic marker in various due to its expression in both normal tissue and tumours.

Normal tissues that express WT-1

WT-1 is expressed in various tissues throughout the body, including:

• Kidney: Essential during fetal kidney development, WT-1 helps form the structure and function of the kidneys.
• Testis: The expression of WT-1 in the male testis it influences germ cell development.
• Ovary: WT-1 is expressed in both the surface epithelium and granulosa cells of the ovary. The surface epithelium covers the ovary and plays a role in protecting underlying cells and responding to hormones, while granulosa cells support oocyte development.
• Uterus: WT-1 is expressed by cells in the myometrium and endometrial stromal cells of the uterus. The myometrium, the muscle layer of the uterus, contracts during childbirth. Endometrial stromal cells are connective tissue cells supporting the endometrium, crucial for menstrual cycle regulation.
• Mesothelium: The mesothelium covers the inside surface of body cavities, such as the pleura (chest) and peritoneum (abdomen), where it provides protection and facilitates organ movements.

Tumours that express WT-1

Several benign (noncancerous) and malignant (cancerous) tumours express WT-1, including:

• Wilms’ tumour: Predominantly seen in children, associated with mutations or deletions in the WT-1 gene.
• Mesothelioma: A cancer linked to asbestos exposure arising from the mesothelial cells of the pleural or peritoneal cavities.
• Ovarian serous carcinoma: A type of ovarian cancer that commonly expresses WT-1. The expression of this protein helps pathologists rule out other types of cancer that can look similar under the microscope.
• Endometrial stromal sarcoma: A type of cancer originating from the connective tissue in the uterus.
• Desmoplastic small round cell tumour: A rare and aggressive type of cancer that often shows WT-1 expression.

How is WT-1 used in pathology?

Pathologists perform a test called immunohistochemistry (IHC) to identify cells expressing WT-1. WT-1 expression is useful for identifying different types of tumours and distinguishing between tumours that look similar when examined under the microscope.

• Distinguishing tumour types: For example, the expression of WT-1 is helpful for differentiating between ovarian serous carcinoma from metastatic cancers to the ovary.
• Identifying mesothelioma: Mesothelioma expresses WT-1, whereas adenocarcinoma or small cell neuroendocrine carcinoma of the lung does not.
• Determining tumour origin: The expression of WT-1 can help narrow the search to organs which normally express this protein such as mesothelium, the ovaries, or the kidneys.

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Atlas of pathology