p63

p63 is a protein that acts as a transcription factor, meaning it helps control when certain genes are turned on or off in cells. It plays a vital role in the development and maintenance of epithelial tissues, which are the layers of cells that line and protect surfaces throughout the body, including the skin, airways, breast ducts, and parts of the urinary and reproductive tracts. p63 is part of the same gene family as p53, a well-known tumor suppressor. It is especially important during early development and helps maintain the structure and function of certain adult cells.

What types of normal cells and tissues express p63?

p63 is normally found in the nucleus of a variety of healthy epithelial cells. These include:

• Squamous epithelial cells such as those in the skin, mouth, and cervix.

• Basal cells in the prostate, respiratory tract, and seminal vesicles.

• Myoepithelial cells in the breast, salivary glands, and sweat glands.

• Urothelial cells in the bladder and urinary tract.

• Thymic epithelial cells.

• Cells in the female reproductive tract, including the cervix and vulva.

In these tissues, p63 helps regulate normal cell growth and repair.

How do pathologists test for p63?

Pathologists test for p63 using a method called immunohistochemistry (IHC). This test uses antibodies that bind to the p63 protein if it is present. When viewed under a microscope, p63 appears as a nuclear stain, meaning the colour change occurs in the nucleus of the cell. A positive p63 result means the protein is present in the tissue sample, while a negative result means it is absent. Pathologists use p63 staining to help identify the type of cells in a tumour and determine where the tumour started.

In some cases, a more specific form of p63 called p40 (also known as ΔNp63) is used because it is more specific for squamous cell cancers, especially in the lung.

What types of tumours express p63?

p63 is found in many types of tumours that arise from epithelial or myoepithelial cells. These include:

• Squamous cell carcinomas of the skin, cervix, vagina, vulva, lung, head and neck, esophagus, and anal canal.

• Urothelial carcinoma (bladder cancer).

• Myoepithelial tumours of the breast and salivary glands, including myoepithelioma, pleomorphic adenoma, and adenoid cystic carcinoma.

• Thymic tumours, such as thymoma and thymic carcinoma.

• Sarcomatoid carcinomas in the breast and bladder.

• Some primary skin adnexal tumours (tumours of sweat glands).

• Merkel cell carcinoma and ALK-negative anaplastic large cell lymphoma (in some cases).

Because p63 is found in many tumour types, pathologists use it in combination with other markers to make an accurate diagnosis.

Why is p63 important in a pathology report?

Testing for p63 helps pathologists determine what kind of cells a tumour is made of and where the tumour may have started. For example:

• In lung cancer, p63 helps distinguish squamous cell carcinoma (usually p63-positive) from adenocarcinoma (usually p63-negative).

• In prostate biopsies, p63 helps differentiate benign prostate tissue (which contains basal cells that express p63) from prostate adenocarcinoma, which typically does not express p63.

• In skin biopsies, p63 can help tell whether a tumour came from sweat glands or from a different part of the body, such as the breast.

• In bladder cancer, p63 can help distinguish urothelial carcinoma from other tumour types, such as those that spread from the prostate.

In addition to helping with diagnosis, p63 expression may also provide prognostic information. For example, loss of p63 has been associated with more aggressive behaviour in certain cancers, such as esophageal squamous cell carcinoma and urothelial carcinoma.

Questions to ask your doctor

• What does the p63 result in my pathology report mean?

• Does the presence or absence of p63 help confirm the type of cancer I have?

• Was p40 also tested, and if so, how does that result help clarify the diagnosis?

• Will the p63 result affect my treatment or follow-up plan?

• Are additional tests needed to confirm the diagnosis?