WT-1 (Wilms’ tumour 1)

WT-1 (Wilms’ tumour 1) is a protein that acts as a transcription factor, meaning it helps control the activity of certain genes within cells. It was initially discovered because of its connection to Wilms’ tumour, a type of kidney cancer commonly seen in children. WT-1 plays an essential role in the normal development and functioning of the kidneys and reproductive organs.

What types of normal cells and tissues express WT-1?

WT-1 is naturally found in several tissues and plays important roles, especially during development.

Tissues that normally express WT-1 include:

• Kidneys: WT-1 is crucial for kidney development during fetal growth, helping to form their structure and function.
• Testis: WT-1 helps in the normal development of sperm cells.
• Ovary: WT-1 is found in ovarian cells, including the epithelium (surface layer) and supportive granulosa cells, both involved in hormone response and egg development.
• Uterus: WT-1 is present in muscle cells, which help with contractions during childbirth, and stromal cells, supporting the inner lining of the uterus.
• Mesothelium: WT-1 is expressed by cells lining the pleura (chest cavity) and peritoneum (abdominal cavity), which helps protect organs and allow smooth organ movements.

How do pathologists test for WT-1?

Pathologists test for WT-1 using immunohistochemistry (IHC). This test involves applying special antibodies to a tissue sample that specifically bind to the WT-1 protein if present. If WT-1 is in the tissue, the antibodies attach to it and cause a visible color change. Pathologists then examine this staining under a microscope to determine if WT-1 is expressed, the types of cells expressing it, and the strength of expression. Cells that express WT-1 are typically described as ‘positive’ while those that do not are described as ‘negative’.

What types of tumors express WT-1?

Both benign (noncancerous) and malignant (cancerous) tumors can express WT-1.

Benign (noncancerous) tumors:

• Some benign ovarian tumors: Some ovarian tumors, such as serous cystadenoma, adenofibroma, and Brenner’s tumor, can express WT-1.

Malignant (cancerous) tumors:

• Wilms’ tumour: A kidney cancer most commonly seen in children, linked with changes in the WT-1 gene.
• Mesothelioma: A type of cancer often associated with asbestos exposure, arising from mesothelial cells in the chest or abdomen.
• Ovarian serous carcinoma: A common type of ovarian cancer expressing WT-1, helpful for distinguishing it from other similar-looking cancers.
• Endometrial stromal sarcoma: A rare cancer originating from connective tissues in the uterus.
• Desmoplastic small round cell tumour: A rare, aggressive cancer frequently showing WT-1 expression.

Why is WT-1 important in a pathology report?

Detecting WT-1 in tumors helps pathologists identify the type and origin of a tumour.

This is particularly helpful in the following situations:

• Identifying ovarian cancer: WT-1 helps distinguish ovarian serous carcinoma from cancers that have spread to the ovary from other locations.
• Diagnosing mesothelioma: WT-1 helps separate mesothelioma from other cancers, such as lung adenocarcinoma or small cell carcinoma.
• Determining tumor origin: WT-1 expression helps pathologists determine whether tumors originated from organs normally expressing this protein, such as the kidneys, ovaries, or the mesothelial lining of body cavities.

Understanding WT-1 expression helps pathologists and doctors provide accurate diagnoses and select effective treatments, guiding patients toward better management of their conditions.