title: Estrogens, estrogen receptors and melanoma.
abstract: The skin is the largest nonreproductive target tissue on which estrogen plays many beneficial and protective roles. Although neither exogenous hormones nor pregnancy represent significant risk factors for melanoma, epidemiological data suggest a higher survival rate in women with metastatic disease versus men and in premenopausal versus postmenopausal patients. Despite the fact that hyperestrogenic signaling has long been implicated in the initiation and progression of several tumors, the role of estrogens in malignant melanoma is still unclear. The cellular effects of estrogens are mediated by two subtypes of estrogen receptors (ERs). Estrogen receptor β (ERβ), the predominant ER in the skin, antagonizes the proliferative action mediated by estrogen receptor α. According to recent immunohistochemical studies, ERβ protein expression decreases progressively with increased Breslow thickness and results in more invasive melanomas; thus, ERβ immunophenotype may distinguish melanomas linked to poor prognosis from those with a favorable course and lead to melanoma unresponsiveness to both estrogen and anti-estrogen treatment. Therefore, if future large-scale immunohistochemical and molecular studies point towards ERβ as an important factor in malignant melanoma progression, they will open up novel and targeted prognostic and therapeutic perspectives.
authors.affiliation: Department of Dermatology, University of Florence, Piazza Indipendenza 11, Firenze 50100, Italy. vincenzo.degiorgi@unifi.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: de Giorgi
authors.forename: Alessia
authors.initials: A
authors.lastname: Gori
authors.forename: Marta
authors.initials: M
authors.lastname: Grazzini
authors.forename: Susanna
authors.initials: S
authors.lastname: Rossari
authors.forename: Federica
authors.initials: F
authors.lastname: Scarfì
authors.forename: Suzanna
authors.initials: S
authors.lastname: Corciova
authors.forename: Alice
authors.initials: A
authors.lastname: Verdelli
authors.forename: Torello
authors.initials: T
authors.lastname: Lotti
authors.forename: Daniela
authors.initials: D
authors.lastname: Massi
mesh_terms: D000818:Animals; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism*; D004967:Estrogens / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008545:Melanoma / Q000453:epidemiology / Q000473:pathology* / Q000628:therapy; D009362:Neoplasm Metastasis; D011379:Prognosis; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000473:pathology* / Q000628:therapy; D013534:Survival
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens