Melanoma outcome seems different between females and males, with a potential protective role of estrogen (E) through estrogen receptors (ER) expression into the tumor. In the study of ERs, both alfa (ERα) and beta (ERβ) is a well-known endocrine elements in non-melanoma tumors, like mammary and endometrial cancer. Immunohistochemistry (IHC) assessment of melanoma concerning ERs represents a path to explore the tumor profile to provide useful information concerning the prognostic and potential adjuvant treatment. Currently, this is not a routine practice, nor a mandatory step for deciding the medical therapy. Typically, IHCs are based on usual kits for mammary tumors regarding ERs configuration. Prior/concomitant use of oral contraceptives and hormonal replacement therapy is not correlated with a better prognostic in melanoma; neither have they represented a contraindication for survivors of melanoma; a subset of tumors might present a higher ER expression which is potentially targeted by the hormone-based treatment as SERMs (Selective Estrogen Receptors Modulator), for instance, tamoxifen. Experimental studies on melanoma cell lines confirmed the anti-tumor activity of ERβ which might function as a prognostic marker. G-protein-coupled estrogen receptors in melanocytes and keratinocytes might be involved, too. Additional crosstalk of TGF-β (Transforming Growth Factor β), respective IGF1 (Insulin-like Growth Factor), and ERα expression are involved in tumorigenic pathways. Recent preclinical studies showed the potential benefits of diarylpropionitrile, a selective agonist of ERβ; pyrazole derivates 21-23 can block ERs. Murine melanoma models showed the interference of anti-estrogenic medication (like molecule fulvestrant) to enhance immune checkpoint blockade, a modern approach to solid cancers. The proliferation of melanoma might be partially explained by ERs; whether this is generally applicable or there is a subgroup of tumors particularly related to E status is still debatable. The subject of E status in melanoma is far from clear at this point and further studies are necessary concerning this particular issue to implement it as a practical approach in the daily management of a disease that still has a very severe prognostic nowadays.
Melanoma is one of the most common types of malignancy in the world, and one known to carry a very poor prognosis until recent years. This review aims to outline the events in the history of the disease and the impact made by the discoveries along the way, as well as the modern-day consensus by referencing the updated literature regarding the present approach and future directions. In the last two decades, several studies and research have brought significant improvement in the diagnosis and clinical management of melanomas. The development of sentinel lymph node biopsy has brought major changes to the surgical approach to the disease, and modern therapies based on recently developed knowledge changed the death sentence this diagnosis once meant to a manageable condition despite its aggressiveness, keeping in mind that early diagnosis and safe margin excision remain the best and most optimistic course of treatment.
