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 αñ. 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. © 2011 Expert Reviews Ltd.
De Giorgi, V., Gori, A., Grazzini, M., Rossari, S., Scarfì, F., Corciova, S., et al. (2011). Estrogens, estrogen receptors and melanoma. EXPERT REVIEW OF ANTICANCER THERAPY, 11(5), 739-747 [10.1586/era.11.42].
Estrogens, estrogen receptors and melanoma
Scarfì, Federica;
2011
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 αñ. 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. © 2011 Expert Reviews Ltd.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.