The Investigation of Somatostatin Receptors as a Potential Target in Breast Phyllodes Tumours

Abstract

ABSTRACTSomatostatin receptors (SSTRs) constitute a family of G protein-coupled receptors that modulate hormonal secretion and regulate cell proliferation and apoptosis upon binding with somatostatin or its synthetic analogues. SSTRs are expressed in most neuroendocrine neoplasms, particularly in gastroenteropancreatic neuroendocrine tumours, and have been utilized as diagnostic markers as well as therapeutic targets. The radioiodinated somatostatin analogue 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Tyr3-octreotate (DOTATATE) has been employed for SSTR-targeting for either diagnostic or therapeutic purposes depending on the labelling with68Gallium or177Lutetium, respectively.SSTR expression is reported in a subset of breast adenocarcinoma and breast neuroendocrine carcinomas; however, minimal knowledge exists regarding their expression in fibroepithelial (biphasic) breast lesions such as fibroadenoma and phyllodes tumours. Aggressive ends of the spectrum, i.e. “cystosarcoma phyllodes” may present a management challenge with recurrences and metastases. In this exploratory study, we investigated both gene and protein expression of SSTR in fibroepithelial lesions of the breast. Our findings reveal that both fibroadenoma and phyllodes tumours express SSTRs. Immunohistochemical analyses suggested that this expression is in the stromal, not epithelial, component by demonstrating that SSTR is predominantly expressed in the areas overlapping with α-smooth muscle actin-positive myoepithelial cells around blood vessels and capillary structures. This study is the first in the literature to demonstrate SSTR positivity in mammary fibroepithelial neoplasms., In a patient undergoing a gallium scan, which is widely used in clinical practice, if a positive lesion is discovered in the breast, the possibility of a fibroadenoma or phyllodes tumour needs to be considered. Once validated, these findings may also have significant implications for the management of these tumours.