Ghrelin as a potential molecular marker of adrenal carcinogenesis: In vivo and in vitro evidence

• Published in: Clinical endocrinology (Oxford) 2018-07, Vol.89 (1), p.36-45
• Main Authors: Komarowska, Hanna, Rucinski, Marcin, Tyczewska, Marianna, Sawicka‐Gutaj, Nadia, Szyszka, Marta, Hernik, Aleksandra, Klimont, Anna, Milecka, Paulina, Migasiuk, Laura, Biczysko, Mateusz, Idasiak‐Piechocka, Ilona, Karczewski, Marek, Ruchala, Marek
• Format: Article
• Language: English
• Subjects: Adenoma; adrenal; Adrenal glands; adrenocortical carcinoma; Carcinogenesis; Diagnosis; Ghrelin; Hyperplasia; IGF2; Insulin-like growth factor II; Neoplasia; Neuroendocrine tumors; Pheochromocytoma; proliferative factor; Statistical analysis; Tumorigenesis; Tumors
• ISSN: 0300-0664; 1365-2265
• DOI: 10.1111/cen.13725

Summary Context Adrenal tumours belong to one of the most prevalent neoplasms. It is a heterogeneous group with different aetiology, clinical manifestation and prognosis. Its histopathologic diagnosis is difficult and identification of differentiation markers for tumorigenesis is extremely valuable for diagnosis. Design To assess ghrelin expression and the relationship among ghrelin, IGF2 and the clinicopathological characteristics of adrenal tumours. To investigate the influence of ghrelin on ACC cell line proliferation. Materials and methods Expression of ghrelin and IGF2 in a total of 84 adrenal tissue samples (30 adenoma, 12 hyperplasia, 8 myelolipoma, 20 pheochromocytoma, 7 carcinoma and 7 unchanged adrenal glands) were estimated. Every operated patient from whom samples were obtained underwent clinicopathological analysis. All the parameters were compared among the groups examined and correlations between these were estimated. H295R cell line was incubated with ghrelin to assess its effect on proliferation and migration rate. Results The highest ghrelin expression was observed in carcinoma samples and the lowest in the control group. Ghrelin expression was 21 times higher in carcinoma (P = .017) and 2.4 times higher in adenoma (P = .029) compared with controls. There were no statistically significant differences between myelolipoma (P = .093) and pheochromocytoma (P = .204) relative to the control. Ghrelin level was significantly higher in carcinoma compared to adenoma (P = .049) samples. A positive correlation between ghrelin and IGF2 expression was observed only in myelolipoma (P = .001). Ghrelin at concentrations of 1 × 10−6 mol/L and 1 × 10−8 mol/L significantly stimulated proliferation and migration rate in the H295R cell line. Conclusion Ghrelin appears to be an essential factor in driving adrenal tumours development.