The CDKN2A gene, located on chromosome 9p21. encodes the p16 protein, a critical tumor suppressor involved in cell cycle regulation. P16 inhibits cyclin-dependent kinases 4 and 6 (CDK4/6), preventing phosphorylation of the retinoblastoma (Rb) protein and arresting the cell cycle at the G1 phase. Loss of p16 function, through deletions, mutations, or promoter methylation, disrupts this checkpoint, promoting uncontrolled cell proliferation—a hallmark of cancer. CDKN2A/p16 alterations are frequently observed in cancers such as melanoma, pancreatic, and lung carcinomas, making it a key biomarker for tumorigenesis and prognosis.
Antibodies targeting p16 are widely used in research and diagnostics to assess protein expression via immunohistochemistry (IHC), Western blotting, or immunofluorescence. In clinical pathology, p16 overexpression is often a surrogate marker for high-risk human papillomavirus (HPV) infection in cervical and head/neck cancers, where viral oncoproteins E6/E7 dysregulate Rb, leading to compensatory p16 upregulation. However, interpretation requires context: some cancers show p16 loss (e.g., gliomas), while others exhibit gain (e.g., HPV-associated tumors). Discrepancies in antibody specificity, epitope recognition, and staining protocols can affect reproducibility, emphasizing the need for validated reagents and standardized methods. Overall, p16 antibodies remain vital tools for understanding cell cycle dysregulation and guiding cancer diagnostics.