DIFFERENTIATION-ASSOCIATED OVEREXPRESSION OF THE CYCLIN-DEPENDENT KINASE INHIBITOR P21(WAF-1) IN HUMAN CUTANEOUS SQUAMOUS-CELL CARCINOMA

p21(waf-1) negatively regulates the cell cycle by inhibiting the activ ity of cyclin-dependent kinases. As p21(waf-1) is a probable tumor sup pressor, we sought to determine whether this cyclin-dependent kinase i nhibitor is abnormally regulated in human cutaneous squamous cell carc inoma (SCC). An immunohistochemical technique was employed to assay p2 1(waf-1) protein in SCCs chosenfrom sun-exposed and anogenital sites. We observed that P21(waf-1) was greatly overexpressed in SCC versus ad jacent benign epithelium. Furthermore, expression of p21(waf-1) was co nsistently elevated in the superficial, differentiated cells versus ba sal keratinocytes, p21(waf-1) expression correlated with the prolifera tive state of the cancers as measured by MIB-1 immunostaining. In vitr o, keratinocytes grown in supplemented media upregulated P21(waf-1)dur ing differentiation, supporting our in vivo observations. We conclude that p21(waf-1) overexpression is associated with differentiation in p roliferating SCC but is not sufficient to suppress cancer development.