SAT-101 Investigating Transcription Factors and Markers Associated with Symptomatic Rathke Cleft Cyst (RCC)

Abstract Disclosure: N. Rzewuska: None. M. Kunicki: None. J. Kunicki: None. Introduction: Rathke's cleft cyst (RCC) is a non-neoplastic and benign lesion of the pituitary gland. Usually, RCCs remain asymptomatic, but in some cases, they could cause symptoms such as headaches, visual impairments, and in 19.4-81% hormonal symptoms. The pathogenesis of RCC remains not fully understood. Experimental studies demonstrated the role of the ISL1 transcription factor in RCC development, which is also expressed in the pituitary's thyrotrope and gonadotrope cell lineages. Abnormal expression of FOXA1 (Forkhead Box protein A1) seems to be involved in cyst development. Pituitary T-box transcription factor (TPIT) and pituitary-specific transcription factor-1 (PIT1) serve as markers for late differentiation of the pituitary gland. Their role has not been explored in the context of RCC. Aim: The study aimed to identify markers characteristic of developing RCC (FOXA1, SOX2, SOX9, CDKN1A) using the immunohistochemical method in the RCC epithelium. We also searched for the usefulness of markers of late pituitary differentiation and routinely used in immunohistochemistry pituitary transcription factors (PIT1, TPIT, GATA3, TTF-1, Erα, Cytokeratin 8) to better understand the etiopathogenesis. Methods: Using the Onko.sys database search engine, we identified 103 patients after searching for "Rathke's cleft cyst." The inclusion criterion comprised symptomatic patients who underwent surgery for RCC in the Neurosurgery Department from 2017 to 2022, where a fragment of the cyst wall was established in histopathology. Among the 73 patients who underwent surgery for symptomatic cysts, 20 cases in which the RCC epithelium was present in the pathological material qualified for immunohistochemical staining with the specified markers. Results: We share the initial findings of our research. The patient group was heterogeneous regarding clinical course and time of observation. We found positive expression of cytokeratin 8, SOX9, and CDKN1A in all tissues (16/16), FOXA1, and SOX2 in most of the cases (14/16), and GATA3 in some RCC tissues (7/16). TTF-1 was positive in only one case, while ER-alpha was positive in three cases. The expression of PIT and TPIT was generally negative in all examined tissues. Conclusions: SOX9 and Cytokeratin 8 may serve as markers for confirming RCC. Additionally, SOX9 and FOXA1 could play a significant role in driving cyst development. The pathological differentiation of cystic pituitary adenoma from RCC can be conducted using PIT and TPIT markers due to their negative staining on the RCC wall. RCC has positive expression of markers of early pituitary development, whereas transcription factors of late differentiation, TPIT, and PIT1, are not expressed in the cyst. The differences in the remaining marker expressions could be examined in a larger cohort and connected to clinical outcomes, such as hormonal manifestations and cyst recurrence. Presentation: Saturday, July 12, 2025