p40 is a specialized protein that helps pathologists identify specific types of cells, especially squamous cells, which are found on surfaces like the skin, the lining of the mouth and throat, and parts of the lungs and urinary tract. p40 is a shortened version (or “isoform”) of another protein called p63, but it is more specific for identifying squamous cells and tumors that come from them. Pathologists test for p40 because it is a reliable marker for diagnosing cancers that show squamous cell differentiation.
p40 is normally found in the nucleus of certain cells, including:
Squamous cells, which line the skin, mouth, throat, lungs, and parts of the urinary tract.
Myoepithelial and basal cells in organs such as the breast, salivary glands, and prostate.
Cytotrophoblasts, which are cells found in the placenta.
In healthy tissue, p40 helps these cells maintain their structure and function.
Pathologists test for p40 using a method called immunohistochemistry (IHC). In this test, special antibodies are applied to a tissue sample, and if p40 is present, the antibodies stick to it and cause a visible colour change. Under the microscope, p40 staining appears in the nucleus of positive cells. If the tumour cells stain strongly and in a large percentage of cells, the result is reported as positive for p40. If no staining is seen, the result is negative.
Pathologists use p40 to help diagnose cancers that involve squamous, basal, or myoepithelial cell types. These tumours often strongly express p40:
Squamous cell carcinoma, regardless of the site (e.g., lung, head and neck, cervix, skin, esophagus, bladder).
Lung cancer: p40 is especially useful in diagnosing lung squamous cell carcinoma, where it is strongly positive in most cases. It is rarely positive in lung adenocarcinoma.
Head and neck cancers, including nasopharyngeal carcinoma, NUT carcinoma, and HPV-related sinonasal cancers.
Salivary gland tumours: myoepithelial carcinoma, adenoid cystic carcinoma, pleomorphic adenoma, and basal cell carcinoma often show strong p40 staining.
Breast cancer: metaplastic carcinomas and myoepithelial tumors may express p40.
Urothelial carcinoma: especially those with squamous features, may show p40 positivity.
Thymic tumors: including thymomas and thymic carcinomas.
Skin and skin adnexal tumors, such as basal cell carcinoma and hidradenoma.
Because p40 is highly specific for squamous cell tumors, it is commonly included in the panel of tests used to subtype non-small cell lung carcinoma and to distinguish squamous cell carcinoma from other cancer types that may look similar under the microscope.
p40 helps pathologists determine the type and origin of a tumour, particularly when it may be a squamous cell carcinoma. This distinction is important because treatment plans for squamous cell carcinoma can differ from other types of cancer, such as adenocarcinoma. For example:
In lung cancer, identifying squamous cell carcinoma with p40 testing helps determine the most appropriate chemotherapy or targeted therapy.
In head and neck tumours, p40 can help confirm that the tumour is squamous in origin and may also provide clues about the underlying cause (such as HPV infection).
In tumours that arise in unusual locations or have unclear features, p40 can help confirm whether the cancer shows squamous, myoepithelial, or basal cell characteristics.
Overall, p40 is a valuable diagnostic tool that helps ensure patients receive an accurate diagnosis and the most appropriate treatment.
What does the p40 result in my pathology report mean?
Does this result confirm a diagnosis of squamous cell carcinoma?
How does p40 help distinguish between different types of cancer?
Will this test result affect my treatment plan?
Are additional tests needed to better understand my diagnosis?