Endocrine Abstracts

Introduction: Ghrelin, a peptide hormone produced in the stomach, stimulates secretion of growth hormone and regulates appetite and energy homeostasis. Various other effects attributed to ghrelin may contribute to many aspects of cancer development and progression.

Material and Methods: Using polyclonal antibody immunohistochemistry, we assessed (by intensity scoring) the immunolocalization of ghrelin in 70 tissue samples, and described particularities within the molecular subtypes of breast cancer. Clinical and histopathological characteristics of the tumors were obtained from patients’ records. Patients histological data was grouped in order to better classify the ghrelin staining characteristics and included primary tumor size (≤ 20 mm; > 20 mm), lymph node invasion (with; without confirmed lymph node invasion), tumor grading, estrogen (ER) and progesterone (PgR) receptor percentage score, intensity score and status (< 1%; > 1% positive in tumor cells), human epidermal growth factor receptor 2 (HER2/neu) status (positive; negative or equivocal), Ki-67 index (< 15%; ≥ 15%) and presence of fibrocystic breast disease.

Results: Ghrelin expression in breast tumor cells correlated inversely with tumor grading (ρ = −0.449, P = 0.020), and positively with estrogen receptor (ER percentage scoring, ρ = 0.221, P = 0.003). Dividing the study group by intrinsic subtypes, a strongly inversely association between ghrelin and tumor size (P = −0.598, P = 0.007), grading (P = −0.849, P = 0.003), and presence of fibrocystic breast disease (P = −0.826, P = 0.033) was observed in triple negative breast cancer cases. Tumor ghrelin and ER percentage scores were positively correlated in luminal B HER2 negative tumors (ρ = 0.121, P = 0.031). For luminal A tumors, a negative association was observed between ghrelin and tumor grading (ρ = −0.364, P = 0.656), lymph node status (ρ = −0.230, P = 0.232), ER (ρ = −0.363, P = 0.188) and PgR (ρ = −0.313, P = 0.241) status, Ki67 index (ρ = −0.489, P = 0.087) and the presence of fibrocystic breast disease (ρ = −0.224, P = 0.656), associations whichdid not reach the level of statistically significance in any of these cases.

Conclusion: Ghrelin regulates several endocrine functions with potential contributions to cancer biology. An endocrine effect of ghrelin, potentially attributable to cancer biology, is its stimulation of growth hormone secretion regulating IGF-1 levels, with subsequent pro-neoplastic effects. However, existing evidence does not strongly support contribution of ghrelin-GH-IGF1 axis to cancer development or progression, but rather prove independent effects. Previous cohort studies reported a positive prognostic significance of ghrelin immunostainings in breast cancer. Furthermore, we showed that ghrelin was linked to better tumor differentiation and proliferation especially in triple negative cases, suggesting a particular mechanism of action and a possible prognostic role of ghrelin in these cases.