Category: Pituitary Disorders/Neuroendocrinology
Pituitary neuroendocrine tumors (PitNETs) are common, mostly benign tumors that exhibit variable invasiveness and risk of recurrence. Whereas biochemical measures are helpful to predict response to therapy and/or recurrence in lactotroph, somatotroph and corticotroph tumors, additional biomarkers that can help predict behavior in clinically non-functioning tumors are needed. The NETest which is a PCR-based MultiAnalyte with Algorithm Analyses test is an in vitro diagnostic biomarker for gastroenteropancreatic- and lung-derived neuroendocrine tumors (NETs) and correlates with tumor R0 resection. We sought to investigate the potential utility of the NETest in pituitary adenomas.
Peripheral blood was collected from consecutive patients undergoing trans-nasal trans-sphenoidal surgery (TNTS) for pituitary tumors (n=145) at UCLA between 2015-2018 in addition to 43 patient controls with other central nervous system (CNS) tumors. The NETest measures the expression of 51 NET marker genes which are then incorporated into a unique algorithm that stratifies the genes based on different “omes” including SSTRome, proliferome, metabolome, secretome, epigenome, and pluromes. Blinded, de-indentified samples were measured at Wren Laboratories.
132/148 (89%) of patients with pituitary tumors had a positive NETest defined as score >20%. All patients with acromegaly had a positive NETest whereas 71/82 (86%) of patients with clinically non-functioning tumors had a positive NETest. The NETest was also positive in 24/43 (55%) of patients with other CNS tumors. All subtypes of pituitary tumors showed a significantly higher NETest score (Mean 44.39 +/- SEM 2.2) compared to meningiomas (Mean 19.8 +/- SEM 3.9) (p<0.001). No correlation of NETest scores with pituitary tumor size or with markers of remission such as prolactin (PRL) level in PRL-secreting pituitary tumors was observed.
This pilot study demonstrates that the NETest is positive in pituitary tumors. It is also positive in other CNS tumors which may in part be explained by the finding that 33% of the NETest genes are associated with neurological diseases. Further in-depth analysis of the various “omes” used for the NETest is ongoing and could provide additional insights into the potential utility of this test in pituitary tumors.
The NETest, while useful for diagnosis and prognosis in gastroenteropancreatic and lung NETs, requires additional evaluation as a biomarker for pituitary tumors.
Carolina Hurtado– Endocrinology Fellow, UCLA Division of Endocrinology, Diabetes and Metabolism, Los Angeles, California
Dongyun Zhang– Assistant Project Scientist, UCLA, Los Angeles, California
Nvard Sisliyan– Volunteer scientist, UCLA
Irvin Modlin– Emeritus Professor, Yale University School of Medicine
Mark Kidd– Laboratory and Scientific Director, Wren Laboratories
Anthony Heaney– Professor, UCLA
UCLA Division of Endocrinology, Diabetes and Metabolism
Los Angeles, California
Endocrinology fellow at UCLA David Geffen School of Medicine. Dr Hurtado attended medical school in Venezuela at Universidad Central de Venezuela, Escuela Luis Razetti and Internal Medicine residency At Icahn School of Medicine at Mount Sinai St. Luke's-West Program.
Assistant Project Scientist
Los Angeles, California
Dr. Zhang has been working at UCLA-David Geffen School of Medicine, Department of Medicine for 5 years focusing on pituitary tumor basic and translational research
Yale University School of Medicine
Emeritus Professor Yale University School of Medicine
Hunterian Prof Surgery, London England
James IV Prof Surgery, Edinburgh, Scotland
Laboratory and Scientific Director
Laboratory and Scientific Director Wren Laboratories LLC
Anthony P. Heaney, MD, PhD is an Associate Professor at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA). His primary areas of clinical and research interest involve the pathogenesis of pituitary tumors and exploiting novel molecular targets to develop innovative treatments for pituitary tumors, and other neuroendocrine tumors.