Searching for Transcription Factors and Markers Involved in Symptomatic Rathke Cleft Cysts (RCC)

Rathke's cleft cyst (RCC) is a benign non-neoplastic lesion of the pituitary gland. It is estimated that 1 in 6 individuals may have an asymptomatic cyst. Typically, these cysts are small (<5 mm) and asymptomatic. As RCC enlarges, it exerts a mass effect, leading to clinical symptoms such as headaches, visual impairments, disturbances in hormonal secretion, and, less commonly, diabetes insipidus. Symptomatic cysts are usually treated surgically, mainly using an endoscopic transsphenoidal approach. However, recurrence of this benign pathology is observed in 16-33% of cases. The pathogenesis of Rathke's cysts has not been fully understood. There is a lack of systematic genetic studies on RCC tissues. To date, no correlation has been established between specific markers considered characteristic of the cyst (cytokeratin 8, SOX2, SOX9, FOXA1, GATA3) and the utility of their assessment in the clinical course. Additionally, Thyroid transcription factor 1 (TTF1) and Estrogen receptor alpha (ER alpha) may potentially play a role in the development of cyst wall. TTF-1 is found positive in tumors arising in the posterior pituitary. ER alpha, in turn, is hypothesized to play a role in developing the anterior pituitary gland, particularly the lactotrophic and gonadotropic cells. Both of these markers were never determined in the cyst wall.

The aim of the study was to determine markers considered characteristic in the development of RCC using immunohistochemical method and to search for their role in the etiopathogenesis of the cysts, also their potential clinical significance.

Using the Onko.sys database search engine, 103 patients were obtained after entering "Rathke's cleft cyst". The inclusion criterion was symptomatic patients operated for RCC in the Neurosurgery Department from January 2017 to January 2022, where a fragment of the cyst wall was found in a histopathological examination. From the group of 73 patients operated on for symptomatic cysts, 20 cases in which the wall of a Rathke cyst was found in the pathological material were qualified for immunohistochemical staining with the above markers.

We present the preliminary results of our study. The patient group was heterogeneous in terms of clinical course. We found positive expression of cytokeratin 8, SOX9 in all cases [16/16], FOXA1, and SOX2 in most of the cases [14/16], while positive expression of GATA3 in some RCC tissues [7/14]. TTF-1 expression was positive in only one case and ER-alpha positive in three cases.

Based on this, it can be concluded that SOX9 and cytokeratin 8 may be the markers to confirm RCC. SOX9 and FOXA1 may have a potential role in driving cyst development. Differences in the expression of the remaining markers could be studied in a larger group and linked to clinical manifestations, including cyst recurrence. This study may address the potential knowledge or role of incompletely known markers in the etiopathogenesis of RCC.

October 17, 2024