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Neuroendocrinology and Pituitary

MON-050 - Proteins Involved in the Neutrophil Degranulation Pathway of Somatotroph Tumors and Correlations with Proliferation and Invasiveness

Monday, June 15, 2026
9:00 AM - 2:00 PM CT
Location: ENDOExpo; Poster Floor


Background: The tumor microenvironment is composed of non-tumor cells, blood vessels, extracellular matrix and soluble factors, and generates a complex network with tumor cells, regulating tumor proliferation, invasiveness, and response to medical therapies.
Patients and methods: A liquid chromatography-mass spectrometry was conducted on samples of somatotroph pituitary tumor (after processing and digestion of the sample) to identify and assay the expression of proteins involved in immune system pathways. The differential expression of identified proteins was compared and investigated according to the tumor pattern of growth, tumor proliferation, and persistence of post-surgery tumor residual. Biological functions were investigated for proteins that were found differentially expressed, with a ratio of variation based on Fold-Change (FC)>|1.50| and statistical significance (p-value < 0.05).

Results: Eleven patients with acromegaly were included. Seven patients were females (63.6%). Mean age at diagnosis was 45 years (SD:18). Mean serum GH levels at diagnosis were 10.5 ng/mL (SD:9.3), and mean IGF-I levels were 2.6xULN (SD:0.8). Ten patients carried a tumor >10 mm (90.9%). An invasive growth was identified in 5 tumors with an invasion of the cavernous sinus (45.4%). Ten patients were diagnosed with a sparsely granulated somatotroph tumor (90.9%). Two tumors (18.2%) were proliferative, as indicated by Ki-67 and p53 expression and the number of mitoses. Six patients (54.5%) underwent curative surgery, and 5 five patients (45.4%) required adjuvant treatment with first-generation somatostatin analogues. In this cohort, a total of 590 proteins were identified. A total of 10 proteins (mainly involved in the neutrophil degranulation pathway) were differently expressed, comparing groups of somatotroph tumors based on established criteria. The proteins 26S proteasome non-ATPase regulatory subunit 3 and mitochondrial antiviral-signaling protein were more expressed in invasive tumors than in non-invasive ones. The proteins phosphoglucomutase-2, keratin, adenylyl cyclase-associated protein 1, and guanylate-binding protein 1 were significantly more expressed in proliferative somatotroph tumors than in non-proliferative ones. The proteins alpha-1-antichymotrypsin, clusterin, phosphoglucomutase-2, glutathione S-transferase omega-1, prosaposin, keratin, and the guanylate-binding protein 1 were significantly more expressed in tumors that underwent radical surgery than in patients carrying a residual disease.

Conclusion: Our results indicate that specific proteins involved in the neutrophil degranulation pathway may impact somatotroph tumor behavior, in terms of invasive growth and proliferation, and consequently, surgical outcome.

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