Expression of retinoic acid receptors in non-neoplastic epithelial disorders of the vulva and normal vulvar skin

Retinoids and their nuclear retinoic receptors (RARs) are important modulat ors of epidermal cell proliferation and terminal differentiation. Aberrant expression of RARs in the epidermis has been found to be associated with al tered differentiation capacity of keratinocytes. In this study, the express ion of the various types of RARs (RAR-alpha, RAR-beta, and RAR-gamma) was i nvestigated in surgical specimens from 17 patients with vulvar lichen scler osus, 12 patients with vulvar squamous cell hyperplasia, and II specimens o f normal vulvar skin by nonradioactive in situ hybridization. The results d emonstrate that RAR-alpha expression is significantly decreased in lichen s clerosus (p < 0.0001) and squamous cell hyperplasia(p = 0.007) compared wit h normal vulvar skin. Furthermore, in normal vulvar skin RAR-alpha mRNA is mainly located in the suprabasal epidermal cell layers, whereas in lichen s clerosus RAR-alpha is expressed predominantly in the basal cell layers. In squamous cell hyperplasia RAR-alpha expression occurs in all cell layers. C ompared with normal vulvar skin, RAR-gamma expression is higher in lichen s clerosus (p = 0.026), but no statistically significant differences are seen in squamous cell hyperplasia. These results suggest that partial loss and abnormal localization of RAR-alpha expression as well as increased RAR-gamm a expression may play a role in the etiology of non-neoplastic epithelial d isorders of the vulva.