SUN-296 Transcriptomic Analysis Of Epithelial Mesenchymal Transition In A Cohort Of Recurrent Pituitary Neuroendocrine Tumors

Abstract Disclosure: A. Moscona-Nissan: None. K. Taniguchi-Ponciano: None. F. Martínez-Mendoza: None. S. Andonegui-Elguera: None. B. Soto-Rocha: None. J. Sidauy-Adissi: None. M. Lisbona-Buzali: None. A. Alegre-Lifhsitz: None. G. Edid-Jaris: None. S. Hinojosa-Alvarez: None. J. Hernandez-Perez: None. R. Chavez-Santoscoy: None. S. Hernández Bustos: None. I. Remba-Shapiro: None. D. Marrero-Rodríguez: None. M. Mercado: None. Introduction: Epithelial-mesenchymal transition (EMT) is a cellular process in which epithelial cells acquire mesenchymal phenotypes, conferring tumors invasive and migratory properties. In PitNETs, EMT is associated with specific clinical features and treatment resistance, while metastatic lesions are infrequent. We aimed to characterize the longitudinal evolution of EMT landscape in paired primary and recurrent PitNETs. Methods: We included 11 patients with paired primary and recurrent PitNETs: 8 non-functioning (NF) gonadotroph adenomas, 1 metastatic corticotroph carcinoma causing Cushing disease, a silent corticotroph tumor, and a somatotroph-cell functioning adenoma. We conducted Whole RNA Sequencing in 22 tumors. We characterized the EMT landscape in this previously studied cohort, using EMTome, a resource for pan-cancer analysis of EMT genes. Differential expression of EMT genes between primary and recurrent tumors was assessed using the Wilcoxon Signed Rank test, with a subgroup analysis of NF PitNETs. We constructed heatmaps and compared expression changes in the carcinoma vs expression changes in other tumors using Z-scores. Results: Canonical transcription factors and signaling pathways driving EMT (SNAI1/2, TWIST1/2, TGFB, CTNNB1, WNT5A, NOTCH1) did not show significant expression changes between primary and recurrent tumors. Additionally, structural genes such as VIM, FN1, and CDH1 did not show significant differences, suggesting that classical EMT pathways are not activated in recurrent PitNETs. Recurrent tumors exhibited downregulation of genes typically increased in EMT such as CDH2 (N-cadherin), and BMP4 (Bone Morphogenetic Protein 4), an enhancer of EMT. Nevertheless, epithelial markers such as ESRP1 (Epithelial Splicing Regulatory Protein 1), EGF, and L1CAM were decreased. Conversely, over-expressed genes in recurrent tumors included CTHRC1 (Collagen Triple Helix Repeat Containing 1), BCL3, MAPK13, and others. In the corticotroph carcinoma, differential expression across the primary vs recurrent tumor revealed over expression of genes such as SSTR5, MAPK13, SPINK5, EGFR, FGF2, ATM, PTEN, and TGFBR3 when compared to the expression change in the rest of tumors though Z-scores; while under expression of L1CAM, ECM, PTTG1, TGFB3, and BCL3 was found. Conclusion: A low or atypical EMT rate may contribute to explain why metastasis from PitNETs is rare. Further research is required to elucidate why pituitary carcinoma is infrequent. Moreover, the recurrent pituitary carcinoma exhibited a distinct expression change in EMT genes compared to the change seen in benign tumors. Presentation: Sunday, July 13, 2025