Cyclin-dependent kinase-4, CDK4-I, p16

CDK4-I is the product of the INK-4 gene. It binds to cyclin 4/6 complexes to control the cell cycle at G1S. It therefore acts as a tumour suppressor gene.

There is increased expression of p16 in both high-grade cervical intra-epithelial neoplasia and in low-grade neoplasia associated with high-risk HPV. There is also immunoreactivity in both cervical glandular intra-epithelial neoplasia and cervical adenocarcinoma.

In most non-small cell carcinomas of lung, inactivation of p16 and/or upregulation of cyclin D1 leads to disruption of the retinoblastoma-mediated of cell cycle arrest. Aberrant p16 methylation is an early event in pulmonary non-small cell carcinogenesis, leading to loss of both p16 activity and expression².

Diagnostic value

Endometrial versus endocervical adenocarcinoma: diffuse positivity favours endocervical carcinoma. Note that benign squamous morules in endometrial adenocarcinoma are commonly positive for p16.
Small cell versus poorly differentiated squamous cell carcinoma of lung ².
In combination with Ki67 in the identification of anal intraepithelial neoplasia.

¹ McCluggage, W. G. (2004). "A critical appraisal of the value of immunohistochemistry in diagnosis of uterine neoplasms." Adv Anat Pathol 11(3): 162-71.

² Zhang H, Liu J, Cagle PT, Allen TC, Laga AC,Zander DS Distinction of pulmonary small cell carcinoma from poorly differentiated squamous cell carcinoma: an immunohistochemical approach. Mod Pathol 2005; 18:111-8

³Kalof AN, Evans MF, Simmons-Arnold L, et al. p16INK4A immunoexpression and HPV in situ hybridization signal patterns: potential markers of high-grade cervical intraepithelial neoplasia. Am J Surg Pathol 2005; 29:674-9

This page last revised 23.7.2006.