Cytokines and chemokines modulate the growth of pituitary adenoma/neuroendocrine tumors: preliminary results of a monocenter prospective pilot study.

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 the expressions of the growth-regulated oncogene (GRO)/CXCL1, thymus- and activation-regulated chemokine (TARC)/CCL17 and epidermal growth factor (EGF) were higher in invasive tumors than in not-invasive ones (respectively p = 0.01, p = 0.002 and p = 0.002). The EGF expression was higher in tumors with a MIB1 > 3% than in those with MIB1 < 3% (p = 0.014). A positive correlation was detected between the expressions of EGF and CXCL1 (p = 0.003, r: 0.7), EGF and GRO-a (p = 0.01, r:0.61), and the number of tumors infiltering CD68 + macrophages and the expression of CCL2 (p = 0.008, r = 0.695).

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.