The p40 antibody, also known as ΔNp63. is a nuclear protein encoded by the TP63 gene, a member of the p53 tumor suppressor family. It specifically targets the N-terminally truncated isoform of p63. lacking the transactivation (TA) domain found in full-length TAp63. p63 plays critical roles in epithelial development, differentiation, and stem cell maintenance. The p40 isoform is predominantly expressed in basal and myoepithelial cells of stratified and glandular epithelia, making it a valuable marker in diagnostic pathology.
In clinical practice, p40 is widely used as an immunohistochemical (IHC) marker to distinguish squamous cell carcinoma (SCC) from other malignancies, particularly adenocarcinoma. For example, in lung cancer diagnostics, p40 positivity strongly supports a diagnosis of lung SCC, while adenocarcinomas are typically negative. Its specificity surpasses that of p63. another p63 isoform, which may cross-react with other p63 variants or neoplasms.
The antibody’s utility extends beyond pulmonary pathology, aiding in the identification of SCCs in head and neck, cervical, and esophageal cancers. Recent studies also explore its role in characterizing basal-like breast cancers and thymic tumors. Despite its diagnostic value, interpretation requires caution, as rare adenocarcinomas or neuroendocrine tumors may show focal positivity. Clone-specific variations (e.g., BC28) and standardized protocols are essential for consistent results. Overall, p40 remains a cornerstone in precise tumor subtyping and treatment planning.