EXPRESSION OF THE HOMEOBOX GENE HOXC4 IN KERATINOCYTES OF NORMAL SKINAND EPITHELIAL SKIN TUMORS IS CORRELATED WITH DIFFERENTIATION

Homeobox (HOX) genes share a highly conserved 183-bp sequence. The enc oded proteins are capable of binding to specific DNA sequences and fun ctioning as transcription factors. HOX genes play a critical role in t he temporal and spatial differentiation of cells during embryogenesis. In several adult tissues, HOX genes are expressed in a constant, tiss ue-specific pattern, whereas in malignant tumors of these tissues an a ltered expression pattern was found. We investigated the expression of HOXC4 in adult normal skin by reverse-transcription polymerase chain reaction and non-radioactive RNA in situ hybridization. Moreover, HOXC 4 expression was studied in various epidermal neoplasms (solar keratos is, six specimens; Bowen's disease, four; squamous cell carcinoma, nin e; basal cell carcinoma, three) by RNA in situ hybridization. HOXC4 wa s found to be expressed in the suprabasal layers of the epidermis in n ormal skin specimens and the adjacent non-lesional epidermis of all ot her specimens. Atypical keratinocytes of solar keratoses and Bowen's d isease as well as basaloid cells of basal cell carcinomas were negativ e. In squamous cell carcinoma, well differentiated areas with keratini zation showed HOXC4 expression, whereas poorly differentiated areas we re negative. Immunostaining with an antibody against cytokeratin 10, a marker of epidermal differentiation, was performed. A good correlatio n between the distribution pattern of HOXC4 and cytokeratin 10 in the lesions examined was found. These results suggest that HOXC4 is expres sed mainly in differentiated keratinocytes. Lack of differentiation (a s in neoplastic cells) is accompanied by downregulation of HOXC4 expre ssion.