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 ERRα, ERRβ and ERRγ 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 ERRα, ERRβ and ERRγ 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 ERRα 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 ERRα staining. A gradual reduction in ERRα cytoplasmic staining was observed from healthy vulvar skin to precursor lesions and further to SCC. Nuclear ERRα staining was observed in 8/33 (24%) LS-dependent and 10/17 (59%) LS-independent SCC samples.


CONCLUSIONS
ERRα, a key regulator of cell energy metabolism, may play a role in the pathogenesis of both LS and vulvar SCC.
Department of Dermatology, Tampere University Hospital, Finland; School of Medicine, University of Tampere, Finland. Electronic address: lagerstedt.maria.e@student.uta.fi.
M
M
Lagerstedt
School of Medicine, University of Tampere, Finland; Fimlab Laboratories, Tampere, Finland.
R
R
Huotari-Orava
Department of Obstetrics and Gynecology, Tampere University Hospital, Finland.
R
R
Nyberg
School of Medicine, University of Tampere, Finland; Department of Obstetrics and Gynecology, Tampere University Hospital, Finland.
J U
JU
Mäenpää
Department of Dermatology, Tampere University Hospital, Finland; School of Medicine, University of Tampere, Finland.
E
E
Snellman
Department of Dermatology, Tampere University Hospital, Finland.
S-L
SL
Laasanen
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002278:Carcinoma in Situ / Q000737:chemistry* / Q000209:etiology; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism*; D012867:Skin / Q000737:chemistry; D014844:Vulva / Q000737:chemistry; D007724:Vulvar Lichen Sclerosus / Q000150:complications / Q000378:metabolism*; D014846:Vulvar Neoplasms / Q000209:etiology / Q000378:metabolism*; D055815:Young Adult; D000097983:ERRalpha Estrogen-Related Receptor
D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor; C490917:ESRRG protein, human; C107914:estrogen receptor-related receptor beta
Estrogen-related receptors; Lichen sclerosus; Vulvar squamous cell carcinoma