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Practical issues in the application of p16 immunohistochemistry in diagnostic pathology
1Department of Pathology and Laboratory Medicine, University of Wisconsin, Madison 53705.
Abstract:
The p16 tumor suppressor gene (CDKN2A) is a member of the INK4 class of cell cycle inhibitors and is located on chromosome 9p21. The p16 protein binds to cyclin-dependent kinases 4 and 6 and maintains the retinoblastoma gene product in its hypophosphorylated state, which in turn binds to E2F transcription factor and prevents cell cycle progression. Expression of p16 protein is increased in aging cells. Immunohistochemistry for p16ink4a is most widely used as a surrogate maker for high-risk human papilloma virus infection in formalin-fixed, paraffin-embedded tissues. The most widely researched, accepted, and practiced use of p16 immunostain is in the lower anogenital tract. In addition, p16 immunostain is widely used for oropharyngeal squamous cell carcinoma. Its applications have also been extended to gynecologic tumors, which are unrelated to human papillomavirus. This article aims to review the literature on the diagnostic utility of p16 immunohistochemistry and highlight the practical issues in the application and interpretation of this stain.
Insights
The p16 tumor suppressor gene (CDKN2A) is a cell cycle inhibitor. P16 immunohistochemistry is a valuable diagnostic tool, particularly for human papillomavirus-related cancers and other tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- The p16 tumor suppressor gene (CDKN2A) encodes a protein that inhibits cell cycle progression by targeting cyclin-dependent kinases.
- P16 protein expression increases in aging cells and is a key regulator of the cell cycle.
- Immunohistochemistry for p16ink4a serves as a surrogate marker for high-risk human papillomavirus (HPV) infection.
Purpose of the Study:
- To review the diagnostic utility of p16 immunohistochemistry.
- To highlight practical challenges in the application and interpretation of p16 immunostaining.
- To explore the expanding applications of p16 immunostain in various cancers.
Main Methods:
- Literature review of studies utilizing p16 immunohistochemistry.
- Analysis of p16 immunostain applications in anogenital and oropharyngeal squamous cell carcinoma.
- Examination of p16 immunostain utility in gynecologic tumors.
Main Results:
- P16 immunostaining is widely used and accepted for diagnosing lower anogenital tract lesions and oropharyngeal squamous cell carcinoma.
- Its application extends to gynecologic tumors, even those not associated with HPV.
- The interpretation of p16 immunostains requires careful consideration of practical issues.
Conclusions:
- P16 immunohistochemistry is a crucial diagnostic marker with established roles in HPV-related cancers.
- The diagnostic utility of p16 immunostaining is expanding to other tumor types.
- Understanding practical aspects of p16 immunostain application and interpretation is essential for accurate diagnosis.
