ECEESPE2025 Poster Presentations Pituitary, Neuroendocrinology and Puberty (162 abstracts)
1Fondazione Policlinico Universitario A. Gemelli, IRCCS, Università Cattolica del Sacro Cuore, Rome, Italy
JOINT2508
Introduction: Cytokine and chemokines have been recognized to be involved in the progression and prognosis of pituitary adenoma/neuroendocrine tumors (PAs/PitNETs), also known as pituitary adenomas. We aim to investigate the expression of cytokine and chemokine in PAs/PitNETs, and their association with PAs/PitNETs clinical and biological behavior.
Patients and methods: A prospective and monocenter study was performed on 16 patients diagnosed for PAs/PitNETs. Cytokine and chemokine were detected on freshly collected PAs/PitNETs samples. Tumor infiltering immune cells were investigated on formally fixed and paraffin-embedded PAs/PitNETs samples. Clinical, biochemical, molecular and morphological data were collected from patients medical records.
Result: Out of 72 patients with PAs/PitNETs that underwent surgical removal at the Neurosurgery Division of our Institution between January and June 2023, sixteen patients were enrolled in the study. Out of 42 cytokines and chemokines that we investigated, we found that all tumors expressed IL-1b, IL-2, IL-3, IL-8, CCL2, EGF, CXCL1, CXCL1 -a, CCL5, SDF1, CCL17, MDC, VEGF, PDGF88 and the leptin. A positive correlation was detected between the intensity score of EGF and CXCL1 (P = 0.003, r:0.7), of EGF and CXCL1-a (P = 0.01, r:0.61); of EGF and CCL5 (P = 0.004, r:0.68); and of CXCL1 and CCL5 (P = 0.003, r = 0.684). An inverse correlation was identified between intensity score of CXCL1 and IL-2 (P = 0.002, r:-0.7). A positive correlation was detected between the number of tumor-infiltering CD68+ macrophages and the CCL2 intensity score (P = 0.008, r = 0.695). No correlation was identified between the presence of circulating anti-pituitary antibodies and presence of tumor cytokines and chemokines. EGF was significantly more expressed in tumors with MIB1>3% (IS:1515 IQR:1642), than in tumor with MIB1<3% (IS: 81 SD: 292, P = 0.014); the IS of the other cytokines/chemokines did not differ in tumor with MIB1<3% and in those with MIB1>3%. Invasive PAs/PitNETs had a higher expression of EGF (IS:465 IQR:1232, P = 0.002), of CXCL1 (IS:1756 IQR:2055, P = 0.01), of CCL17 (IS:351 IQR:609, P = 0.002) then not invasive PAs/PitNETs (EGF IS:260, IQR:520; GRO:718 IQR:890; CCL17:147, IQR:443). PAs/PitNETs with invasion of the cavernous sinus expressed higher levels of EGF (IS:652 IQR:1457, P = 0.004), of CXCL1 (IS:2170 IQR:2308, P = 0.02) and lower IL-2 levels (IS:326 IQR:729, P = 0.02), then not invasive cavernous sinus PAs/PitNETs (EGF IS:212 IQR:476; CXCL1 IS: 719 IQR:859, IL-2 IS:326 IQR:729).
Conclusion: Our preliminary results support that in PAs/PitNETs, the cytokines and chemokines generate an immune network, that may contribute to regulating the cell proliferation and pattern of growth.