FRI296 Somatostatin Receptor 5 Staining In Prolactinomas
Authors: Mehta Sonal , Feelders Richard Abraham , Hofland Leo J , Campana Claudia , Neggers Sebastian J CM M , Li Xiaochun , Wright Kyla , Skwiersky Samara , Goldberg Judith D , Kim Hyon , Zagzag David , Agrawal Nidhi 
Published: October 2023

Abstract
Disclosure: S. Mehta: None. R.A. Feelders: Advisory Board Member; Self; Corcept. Research Investigator; Self; Recordati, Strongbridge. L.J. Hofland: None. C. Campana: None. S.J. Neggers: None. X. Li: None. K. Wright: None. S. Skwiersky: None. J.D. Goldberg: None. H. Kim: None. D. Zagzag: None. N. Agrawal: Research Investigator; Self; Chiasma, Ascendis, Recordati.
The vast majority of prolactinomas are treated with dopamine agonists (DA) with excellent response, however DA resistance occurs in about 15% of prolactinomas. Surgery and radiotherapy are alternative treatments for these patients, but are not always successful. Somatostatin (SST) receptors have been studied with growing interest in prolactinomas. There are five SST receptor subtypes and mRNA expression analysis of prolactinomas has shown high expression of SST5 in comparison to SST1 and 2. The somatostatin analog, Pasireotide, which has a 40-fold greater binding affinity to SST5 compared to SST2 receptors, shows promising results in individual case reports of DA resistant and aggressive prolactinomas. This two-center retrospective cohort study investigated dopamine 2 (D2R), SST2a and SST5 receptor expression in surgical specimens of DA resistant prolactinomas. The study included consecutive surgical cases of adult patients with a diagnosis of DA-resistant prolactinoma at NYU Langone Health and Erasmus MC. DA resistance was defined as a failure to achieve normal prolactin (PRL) levels on maximally tolerated dopamine agonist doses and/or a failure to achieve 50% reduction in tumor size on coronal view. Co-secreting pituitary tumors were excluded to keep the somatostatin receptor analysis specific to prolactinomas. Receptor expression was scored on the basis of the well validated immunoreactivity score (IRS). This was done independently by two investigators by calculating the product of the percentage of positive cells and the intensity of the staining. 34 patients with average age 41.6 years and 19 (56%) males and 15 females are included in this analysis. Results: means (SDs) of pre-op PRL, pre-op image tumor size transverse and post-op PRL follow-up are respectively 1796 (4772) ng/mL in 33 patients; 2.23(1.61) cm in 15 patients; 108 (117) ng/mL in 17 patients. 31/33(94%) patients used DA preoperatively at various doses; 25/34 (74%) were DA resistant. Other indications include DA intolerance, apoplexy, cerebrospinal fluid leak. D2R was expressed in 94.1% (95% CI: 80.8%, 99.2%) of the cases. SST5 is expressed 61.8% (95% CI: 43.6%, 77.9%) of the prolactinomas and at a high level in a subset of SST5 positive cases. Only 17.6% (95% CI: 6.7%, 34.5%) of the prolactinomas express SST2a. SST5 expression has previously been studied in prolactinomas with variable expression. We show in this retrospective two center study a higher expression of SST5 receptor staining than previously demonstrated analyses and suggest SST5 staining to consider Pasireotide use in a subset of these patients. Larger prospective studies are needed to validate these findings.
Presentation: Friday, June 16, 2023