ECE2020 Oral Communications Hot Topics (including COVID-19 (7 abstracts)
Expression of estrogen-related receptors and epidermal growth factor receptor in normal adrenal cortex and adrenocortical tumors: A possible role of GPR30 and EGFR in adrenocortical malignancy
Christos Parianos 1 , Georgios Kyriakopoulos 2 , Narjes Nasiri-Ansari 3 , Angeliki Karapanagioti 3 , Anna Angelousi 4 , Chrysanthi Aggeli 1 , Giorgos Zografos 1 , Theodosia Choreftaki 5 , Theodora Kounadi 6 , Harpal Randeva 7 , Gregory Kaltsas 8 , Athanasios G Papavassiliou 3 & Evanthia Kassi 3,8
1General Hospital of Athens “G. Gennimatas”, 33rd Department of Surgery, Athina, Greece; 2Evaggelismos General Hospital, Department of Pathology, Athina, Greece; 3National and Kapodistrian University of Athens, Faculty of medicine, Department of Biological Chemistry, Athina, Greece; 4National and Kapodistrian University of Athens, Medical School, Laiko General Hospital, Athina, Greece; 5General Hospital of Athens “G. Gennimatas”, Department of Pathology , Athina, Greece; 6General Hospital of Athens “G. Gennimatas”, Department of Endocrinology and Diabetes Center, Athina, Greece; 7Warwick Medical School, Division of Translational and Experimental Medicine- Metabolic and Vascular Health, United Kingdom; 8National and Kapodistrian University of Athens, Medical School, Endocrine Unit, 1st Department of Propaedeutic Medicine, Athens, Greece
Introduction: The majority of adrenal neoplasms are benign while adrenocortical carcinomas (ACC) are rare with poor prognosis. Previous studies indicated that estrogens play important role in the etiology and progression of adrenocortical tumors. Estrogens exert genomic activities trough the estrogen-receptor (ER) subtypes α and β, while the non-genomic effects are mediated by membrane-bound-G-protein-coupled-ER-30 (GPR30). Although estrogens induce cancer cell proliferation through ERα, ERβ appears to exert a protective effect. In vitro experiments showed that treatment with ERα antagonist as well as GPR30 agonist reduces proliferation in H295R cells. However, data on the expression profile of ERs in normal and human adrenocortical neoplasms are limited. Epidermal growth factor receptor (EGFR) found to be highly expressed in ACC. The expression of EGFR has been negatively correlated with expression of ER in other cancers, while data regarding the correlation between ERs and EGFR expression in adrenocortical neoplasms are missing.
Aim: We aimed to investigate the expression profile of ERs and EGFR in adrenocortical neoplasms and correlate it with their biological behavior.
Material and Methods: Total RNA was extracted from fresh frozen tissue of: eight non functional adenomas (NFA), eight cortisol producing adenomas (CPA), their adjacent normal adrenal tissues (NAC) AND eight adrenocortical carcinoma (ACC). The expression of ERα, ERβ, GPR30 and EGFR genes was evaluated by qPCR. The Immunohistochemistry (IHC) was performed to evaluate the EGFR and GPR30 protein levels.
Results: The expression of both ERα and GPR30 were higher in the CPA as compared to their adjacent normal tissue (P < 0.05) while there was no significant difference in ERβ and EGFR mRNA levels between CPA, NFA and their adjacent normal tissues. The expression of GPR30 was significantly higher in ACC compared to either NFA or NAC groups (P < 0.05), and marginally higher in ACC compared to CPA. The expression of ERα and EGFR was higher in ACC compared to either CPA or NFA (P < 0.1). IHC confirmed the higher expression EGFR in ACC compared to the adrenal benign tumors. A marginal positive correlation between EGFR and GPR30 expression was observed in ACC.
Conclusion: To our knowledge this the first study to evaluate the expression of membrane-bound GPR30 in human adrenocortical neoplasms. Our preliminary data suggest a possible role of GPR30 and EGFR in adrenocortical malignancy, while ERα may play a role in functional adenomas. Further studies with larger number of samples are required to elucidate the role of ERs and EGFR on the adrenal tumorigenesis.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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