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Neuroendocrinology and Pituitary

MON-043 - Senescence, Epithelial-Mesenchymal Transition and Stemness Landscapes of Aggressive and Treatment-Resistant Pituitary Tumors

Monday, June 15, 2026
9:00 AM - 2:00 PM CT
Location: ENDOExpo; Poster Floor
Disclosure(s):
Moises Mercado, MD: No financial relationships to disclose
Although most pituitary tumors (PT) are histologically benign, they frequently behave aggressively, invading surrounding structures and recurring despite multimodal therapy. Although the molecular pathogenesis of aggressive PT is still largely unknown, certain distinctive molecular features are known to play a role, including the expression of genes associated with epithelial-mesenchymal transition (EMT), as well as the presence of stem cells and tumoral cells showing a senescent phenotype. To further explore the molecular landscape of these pituitary aggressive lesions, we carried out spatial transcriptomics in 8 therapy-resistant prolactinomas, as well as single nucleus RNA sequencing in 2 somatotrophinomas and 4 nonfunctioning gonadotrophinomas.
All samples showed a high degree of intratumoral heterogeneity, with 2-10 transcriptional clusters. Senepy analysis revealed that all tumors harbored a low and a high senescence cluster. Senescence markers such as β-galactosidase, p27, p16 and p21were all expressed in both, high and low senescence clusters, with a slightly higher expression in the former. PT are comprised by terminally differentiated cells (expression of GH or PRL and POU1F1 mRNA for the somatotrophinomas and prolactinomas, and of FSH/LH and NR5A1 mRNA for nonfunctioning gonadotrope tumors), and a very small number of oligopotent and multipotent cells (expression of SOX2, LGR4 and RBPMS mRNA).
PI3K-cascade-FGFR1 and inositol phosphate metabolism, were mainly altered in prolactinoma clusters with a low senescence score; the somatotrophinomas showed alterations in phosphatidyl inositol signaling and serine/threonine kinase activity, whereas the gonadotrophinomas displayed alterations in sphingolipid signaling and serine/threonine kinase alterations. In conclusion, PT consist of terminally differentiated cells with a senescent phenotype and with alterations in genes involved in lipid metabolism.

*Unless otherwise noted, all abstracts presented at ENDO must not be released to the press or the public until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.*