Expression of retinoic acid receptor proteins in basal cell carcinomas: an immunohistochemical analysis

We analyzed immunohistochemically the expression of RAR proteins in basal cell carcinomas (BCCs; n = 15) in situ. The labeling pattern for the different types of RARs was compared with the staining pattern of the proliferation marker Ki-67 in the same tumors. We found strong immunoreactivity for RAR-alpha and moderate immunoreactivity for RAR-gamma in all BCCs analyzed, whereas no or very weak staining for RAR-beta protein was detected. In contrast to RAR-gamma, which revealed no or only marginal differences in staining intensities, RAR-alpha immunoreactivity was consistently stronger in BCCs compared to adjacent unaffected epidermis. In general, labeling of BCCs for RAR-alpha and RAR-gamma was pronounced in cells of the palisade and peripheral cells, whereas staining in the center of the tumors was heterogeneous. Eleven of the 15 BCCs analyzed revealed no visual correlation in comparing labeling patterns for RAR-alpha and RAR-gamma with the labeling pattern for Ki-67. In four specimens, expression of RAR-alpha, RAR-gamma, and Ki-67 proteins was confined to peripheral tumor cells. Our findings indicate that (a) RAR-alpha and RAR-gamma proteins are, in contrast to RAR-beta, strongly expressed in BCCs; (b) expression of RAR-alpha is upregulated in BCCs compared to keratinocytes of uninvolved epidermis; and (c) BCCs may be targets for potentially preventive or therapeutic treatment with RAR-alpha- or RAR-gamma-selective retinoic acid metabolites.