p16

p16 is a tumour‑suppressor protein encoded by CDKN2A and functions as a cyclin‑dependent kinase inhibitor that prevents G1–S cell‑cycle progression. In IHC, p16 expression is widely used as a surrogate marker for high‑risk HPV–driven lesions because HPV E7–mediated inactivation of RB leads to p16 overexpression. Diffuse ‘block‑type’ nuclear and cytoplasmic positivity supports an HPV‑associated process, especially in anogenital lesions (cervical, vulva, vaginal, anal, penile) and HPV‑related oropharyngeal squamous cell carcinoma. However, p16 overexpression can also occur through HPV‑independent RB‑pathway dysregulation in several tumours, including liposarcoma, gastric adenocarcinoma, lymphomas, pulmonary adenocarcinoma, neuroendocrine carcinoma, and subsets of uterine carcinomas. Its greatest utility is in distinguishing high‑grade intraepithelial lesions and in differentiating cervical adenocarcinoma (typically p16‑positive) from endometrial adenocarcinoma (often negative or patchy staining)(1-4).

Recommended Controls

Criteria for acceptable staining is nuclear and cytoplasmic. The recommended control is to include a cervical adenocarcinoma as a high expressor for staining in all tumour cells and tonsil (negative – vast majority of lymphocytes and positive – crypt epithelial cells).

Expected staining pattern

Cervical cancer (ALK Phos Detection kit)

Cervical cancer (DAB Detection kit)

Tonsil

Disclaimer

These methods are intended as a guide only. Laboratories that wish to implement these methods should perform internal validation/verification prior to use. The RCPAQAP does not make any claim or warranty for the accuracy or performance of these methods.