Expression of p21 (Waf1/Cip1) in head and neck cancer in relation to proliferation, differentiation, p53 status and cyclin D1 expression

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Abstract
P21 (Waf1/Cip1) is a critical downstream effector in the p53-dependent pathway of growth control and causes growth arrest through inhibition of cyclin-dependent kinases. In this study 67% of 43 head and neck squamous cell carcinoma (HNSCC) and 60% of 15 tumour-adjacent oral dysplasias overexpressed p21 by immunohistochemical staining. Overexpression of p21 in HNSCC was independent of the presence of functional p53, as assessed by analysis of mutations and loss of heterozygosity and by immunohistochemistry. Rather, the expression pattern of p21 was associated with differentiation. Furthermore, in most tumours, the p21 positive cells did not incorporate bromodeoxyuridine (BrdU), which indicates inhibition of proliferation by p21 in these cells. In some tumours, p21 was also expressed in proliferating cells. In these latter tumour cells, cyclin D1 was frequently expressed as well. Therefore, we suggest that expression of cyclin D1 might overcome the inhibitory effect of p21 in these cells.