Differentiation-associated overexpression of the cyclin-dependent kinase inhibitor p21waf-1 in human cutaneous squamous cell carcinoma.

p21waf-1 negatively regulates the cell cycle by inhibiting the activity of cyclin-dependent kinases. As p21waf-1 is a probable tumor suppressor, we sought to determine whether this cyclin-dependent kinase inhibitor is abnormally regulated in human cutaneous squamous cell carcinoma (SCC). An immunohistochemical technique was employed to assay p21waf-1 protein in SCCs chosen from sun-exposed and anogenital sites. We observed that p21waf-1 was greatly overexpressed in SCC versus adjacent benign epithelium. Furthermore, expression of p21waf-1 was consistently elevated in the superficial, differentiated cells versus basal keratinocytes. p21waf-1 expression correlated with the proliferative state of the cancers as measured by MIB-1 immunostaining. In vitro, keratinocytes grown in supplemented media upregulated p21waf-1 during differentiation, supporting our in vivo observations. We conclude that p21waf-1 overexpression is associated with differentiation in proliferating SCC but is not sufficient to suppress cancer development.