Expression patterns of estrogen receptors [ERα, ERβ, and G-protein associated ER (GPER)] in melanoma and skin may suggest their differential roles in carcinogenesis. Phytoestrogenic compound cyanidin-3-o-glucoside (C3G) has been shown to inhibit the growth and metastatic potential of melanoma, although the underlying molecular mechanism remains unclear. The aim of this study was to clarify the mechanism of action of C3G in melanoma in vitro and in vivo, as well as to characterize the functional expressions of ERs in melanoma. In normal skin or melanoma (n = 20/each), no ERα protein was detectable, whereas expression of ERβ was high in skin but weak focal or negative in melanoma; and finally high expression of GPER in all skin vs. 50% melanoma tissues (10/20) was found. These results correspond with our analysis of the melanoma survival rates (SRs) from Human Protein Atlas and The Cancer Genome Atlas GDC (362 patients), where low ERβ expression in melanoma correlate with a poor relapse-free survival, and no correlations were observed between SRs and ERα or GPER expression in melanoma. Furthermore, we demonstrated that C3G treatment arrested the cell cycle at the G2/M phase by targeting cyclin B1 (CCNB1) and promoted apoptosis via ERβ in both mouse and human melanoma cell lines, and inhibited melanoma cell growth in vivo. Our study suggested that C3G elicits an agonistic effect toward ERβ signaling enhancement, which may serve as a potential novel therapeutic and preventive approach for melanoma.

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Summary Sarcoidosis is an inflammatory, multisystem disease with an undetermined etiology. The presence of noncaseating granulomas in involved organs is a characteristic pathomorphological feature. Sarcoidosis, like a chameleon, can mimic different medical conditions. Although the lungs are most commonly involved, extrapulmonary manifestations can influence any system. The clinical course of the disease may differ. Immediate initiation of glucocorticosteroid therapy is important when critical organs are impaired. A case of a patient with sarcoidosis whose first clinical symptoms were related to diabetes insipidus (DI) was presented. The diagnosis of multiple organ sarcoidosis was delayed because of an adequate response to treatment with vasopressin. The multidisciplinary diagnostic approach validated the involvement of the pituitary gland, lungs, lymph nodes, bones, and subcutaneous tissue. The presented case emphasizes the critical importance of the multifaceted differential diagnosis of patients with DI. Learning points Sarcoidosis usually affects the lung but can also be a multisystemic disease. The assessment of the extension of sarcoidosis remains complex. A multidisciplinary approach must identify all-organ involvement and initiate appropriate sarcoidosis treatment. Diabetes insipidus (DI) can be the first symptom of a systemic granulomatous disorder. In the differential diagnosis of DI, a comprehensive assessment of rare causes of endocrine disorders, including extrapulmonary sarcoidosis, should be considered.