Reduction in ERRα is associated with lichen sclerosus and vulvar squamous cell carcinoma

Objective. ERRS (estrogen-related receptors) regulate energy metabolism, the cell cycle and inflammatory processes in both normal and cancer cells. Chronic inflammation induced by lichen sclerosus (LS) or human papilloma virus (HPV) precedes vulvar squamous cell carcinoma (vulvar SCC). We investigated the expression of ERR alpha, ERR beta and ERR gamma in normal vulvar skin, LS as well as LS-dependent and LS-independent/HPV-related vulvar SCC. Methods. A total of 203 samples were analyzed for ERR alpha, ERR beta and ERR gamma by using immunohistochemistry. These included 37 normal vulvar skin samples, 110 LS samples, 6 vulvar intraepithelial neoplasia (VIN) samples and 50 vulvar SCC samples. Results. A substantial reduction in or disappearance of ERR alpha was detected in all vulvar SCC samples. A total of 79% of childhood-onset LS and 51% of adulthood-onset LS lesions showed decreases in ERR alpha staining. A gradual reduction in ERR alpha cytoplasmic staining was observed from healthy vulvar skin to precursor lesions and further to SCC. Nuclear ERR alpha staining was observed in 8/33 (24%) LS-dependent and 10/17 (59%) LS-independent SCC samples. Conclusions. ERR alpha, a key regulator of cell energy metabolism, may play a role in the pathogenesis of both IS and vulvar SCC. (C) 2015 Elsevier Inc. All rights reserved.