Spatial analysis of p63, K5 and K7 defines two groups of progenitor cells that differentially contribute to the maintenance of normal sebaceous glands, extraocular sebaceous carcinoma and benign sebaceous tumors.

The histogenesis of extraocular sebaceous carcinomas is - in contrast to ocular sebaceous carcinomas - unclear, and information about the exact cellular architecture of these lesions and even of the normal sebaceous gland is still scarce. This study attempts to elucidate the histogenesis of sebaceous tumors, using multicolor immunofluorescence stainings to analyze 21 cases of sebaceous tumors (six each of extraocular sebaceous carcinoma, sebaceous adenoma and sebaceoma, and three cases of steatocystomas) and eight cases of normal sebaceous glands for p63, several keratins, androgen receptor, adipophilin, epithelial membrane antigen (EMA) and Ki-67. The data of this observational study provide evidence for the existence of two subpopulations of progenitors in normal sebaceous glands: (i) p63(+) K5(+) progenitors which generate the K10(+) luminal cells of sebaceous ducts; and (ii) p63(+) K5(+) K7(+) progenitors which finally generate K7(+) adipophilin(+) EMA(+) sebocytes. Without exception, all types of sebaceous tumors contained p63(+) K5(+) cells. Furthermore, these tumors showed a cellular hierarchy and differentiation to adipophilin(+) and/or EMA(+) mature sebocytes and to K10(+) ductal cells through intermediary cells. Notably, a considerable number of sebaceous tumors lack the K7 pathway of cell maintenance in the normal sebaceous lobule. Based on our data, we propose a cellular algorithmic model of the hierarchy of normal sebaceous glands and of sebocytic tumors in which p63(+) K5(+) cells play a major role.