Loss of p21(WAF1) compartmentalisation in sebaceous carcinoma compared with sebaceous hyperplasia and sebaceous adenoma.

AIMS Regulation of cell cycle progression is a fundamental control process, linked to cellular differentiation and apoptosis in normal tissues. p21(WAF1) is a nuclear protein that regulates cell cycle progression. p21(WAF1) can be transcriptionally upregulated by p53, but may be activated independently of p53-for example, during terminal differentiation. Loss of topological control of p21(WAF1) expression is an early feature of malignancy in the colorectal system. Similar to the colonic mucosa, sebaceous glands contain cells that are constantly going through a process of cell division, differentiation, and cell death. This study investigated the expression of p53, p21(WAF1), and the proliferation marker Ki67 in normal sebaceous glands, sebaceous adenoma, sebaceoma, and sebaceous carcinoma. METHODS Serial sections were stained with monoclonal antibodies to p21(WAF1), p53, and Ki67 (MIB1) using standard immunohistochemical techniques. RESULTS In normal sebaceous glands, p21(WAF1) positive cells were only seen within the differentiating compartment, which was spatially distinct from the cycling peripheral Ki67 positive cells. In sebaceous adenoma and sebaceoma, topological control was maintained, with the distribution of markers being similar to that seen in normal sebaceous glands. Loss of topological control of markers of cellular control was seen in sebaceous carcinoma only. This contrasts with colonic tumours, in which loss of p21 compartmentalisation is seen in adenomas at an early stage of tumour progression. CONCLUSION This work confirms the hypothesis that the dysregulation of cell cycle progression is an important process in the development of malignancy within sebaceous glands, although loss of topological control was seen only in sebaceous carcinoma.