Female melanoma and estrogen receptors expression: an immunohistochemical pilot study

Abstract

Epidemiologic data highlight sex differences in melanoma outcome. A putative role of sex hormones is still under investigation. Very few laboratory investigations have focused on the level of expression of estrogen receptors in melanoma. We evaluated the presence of estrogen receptors alpha (ERα) and beta (ERβ) in melanoma specimens from female patients with a previous history of breast carcinoma (BC). Moreover, another group of female patients undergoing ovarian stimulation (OS) were also compared to two control groups matched for age and melanoma staging. The study was performed at the IRCCS Policlinico di Sant’Orsola Hospital’s Melanoma Unit from January 2017 to December 2019. The nuclear and cytoplasmatic immunohistochemical staining was evaluated and scored by the percentage of stained tumour cells: 0 (≤20%), 1 (21–50%) or 2 (≥50%). Twenty-eight specimens were analysed. ERβ nuclear presence was detected in all cases of women with a history of breast cancer. Cytoplasmatic ERβ was clearly expressed with a score of 2 in seven cases. In the respective control group, nuclear and cytoplasmatic ERβ expression was much lower. A cytoplasmatic ERα positivity was also detected in almost all cases. In the second group of women who experienced ovarian stimulation for Assisted Reproductive Technology (ART), a lower abundance of nuclear ERs was detected. Conversely, cytoplasmatic ERβ and α expression ranged widely. Melanoma of women treated with anti-estrogen therapy is generally more prone to express estrogen receptors compared with women of the same age and CM staging but also compared with women in fertile age with and without a history of OS.

PRAME Expression in Mucosal Melanoma of the Head and Neck Region

“…It is possible that the peculiar role of sex hormones (androgen and estrogen) in the development of melanomas, as well as the complex intracellular mechanisms regulated by these 2 molecules, could explain the different PRAME expression observed in females and males. 45,46 To conclude, the data here obtained indicate that PRAME is a useful tool for the…”

“…It is possible that the peculiar role of sex hormones (androgen and estrogen) in the development of melanomas, as well as the complex intracellular mechanisms regulated by these 2 molecules, could explain the different PRAME expression observed in females and males. 45 , 46 To conclude, the data here obtained indicate that PRAME is a useful tool for the appropriate diagnosis of MBML-H&N and MM-H&N. The most reliable score to differentiate MM-H&N and MBML-H&N is that proposed by Raghavan and colleagues (< 60% vs. ≥60% of PRAME-positive cells), but a subgroup of specifically sited MM-H&N (palate) can be PRAME-negative (although this assumption is based on a low number of cases and future studies are needed to verify this finding). High PRAME expression (≥60%) was found in association with specific mucosal sites, nodular histotype, and female sex, suggesting a distinct involvement of this molecule in the pathogenesis of these subgroups of tumors.…”

Possible Association Between Melanoma Arising from Congenital Naevus and Oestrogen or Progesterone Receptor Expression: Clinicopathological Analysis

“…Sex hormone receptor expression is induced during pregnancy or while using oral contraceptives, which may increase the risk of melanoma development and may be associated with pigment changes in melanoma precursor lesions (5). However, the association between hormone receptor expression and melanoma development is cont-radictory (6)(7)(8)(9)(10). Recent studies investigating G protein-coupled oestrogen receptor (GPER) on cultured melanoma cells have shown that selective GPER activation induced long-term changes that maintained a more differentiated cell state, increased pigment production, decreased proliferative capacity, and decreased expression of the onco-driver and stem cell marker c-Myc (11).…”

Approach of Multiple Endocrine Neoplasia Type 1 (MEN1) Syndrome–Related Skin Tumors

“…Despite potential menin involvement in the development of melanoma, germline MEN1 mutations are not prone to this malignancy, as, for instance, has been found with other genes such as CDKN2A [ 93 , 126 , 127 ]. Other hormonal dysfunctions involving growth factors, growth hormone–IGF-1 axes, or estrogens/estrogen receptor status have been reported in melanoma without a clear connection to endocrine tumors underlying MEN1 [ 128 , 129 , 130 , 131 , 132 , 133 ]. Larger clinical studies on MEN1 and potential skin involvement are necessary, including longitudinal data and comparison with patients without dermatological issues.…”

“…Finally, the present topic of following the skin tumors in MEN1 represents a fraction of a more complex picture that includes cutaneous aspects in association with various tumor-related hormonal issues as seen in acromegaly, primary hyperparathyroidism, or similar findings in pancreatic NETs in addition to heterogeneous anomalies in MEN2 syndrome (involving both MEN2A and MEN2B type, such as dermal hyperneury, cutaneous lichen amyloidosis, sclerotic fibromas, atypical rash, macular amyloidosis, etc. ), but also, clinical expression of carcinoid syndrome caused by gastroenteropancreatic NETs or metastatic medullary thyroid cancer [ 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 ]. A good dermatological—endocrinological collaboration is required to benefit our patients.…”