ODP293 Aberant Expression of SF-1 Transcription Factor in ACTH-secreting Pituitary Tumors: Possible Association With Aggressive Disease Evolution

Cushing's disease represents a rare endocrine disorder caused by hypercortisolism due to an ACTH-secreting pituitary tumor. Pituitary adenomas (PAs) are mostly benign tumors but may have features of invasiveness and aggressiveness. They are clinically classified by their hormone-secreting characteristics. Expression of pituitary hormones in adenohypophyseal cells is controlled by several transcription factors (PIT1 for GH, PRL and TSH lineage, SF1 for gonadotroph lineage and TPIT for ACTH lineage). Eight cases of Cushing's disease (CD) were included in the current study. The diagnostic was sustained by clinical features, hormonal assessment, and radiological findings (pituitary CT or MRI). All patients underwent surgical removal of pituitary tumor using transsphenoidal resection. All tissue specimens were evaluated using histological routine staining (hematoxylin and eosin) and immunohistochemical staining for vimentin, pituitary hormones (GH, PRL, TSH, FSH, LH, ACTH), and transcription factors (PIT1, TPIT, SF1). The intensity IHC scores ranged from 0 to 3+ and a staining higher than 30% (2+) was considered positive for interpreting the results. Based on the histopathological and immunohistochemical data correlated with the evolution of the disease (remission versus persistent disease), five molecular subgroups were identified. Subgroups 1 to 3 had a positive expression of ACTH and TPIT, with variations regarding SF1 expression: there was no expression in subgroup 1, nuclear positivity in 2, and cytoplasmic reaction in 3. Subgroups 4 and 5 consisted of plurihormonal adenomas with unusual immunohistochemical combination. They had IHC positive score for ACTH, GH, TPIT and were differentiated by the expression of SF1: lack of expression in subgroup 4 and intense cytoplasmic reaction in 5. The expression of SF1 was linked to the evolution of the disease, patients from subgroups which did not have SF1 cytoplasmic reaction (1, 2, 4) had remission of CD, while patients in subgroups 3 and 5 had persistent disease (including one case who evolved to exitus due to cardiovascular complications of the severe hypercortisolism). Transcription factors evaluation is important for classifying pituitary adenomas and finding clinicopathological correlations with the aim of providing a better therapeutical approach. In the current study, although SF1 is a marker of gonadotroph lineage (1), its aberrant cytoplasmic expression in CD may contribute to an aggressive evolution and to other cell lineage differentiation (PIT1, TPIT). Neou M et al, Pangenomic Classification of Pituitary Neuroendocrine Tumors. Cancer Cell. 2020 Jan 13;37(1): 123-134. e5. doi: 10.1016/j. ccell.2019.11. 002. Epub 2019 Dec 26. PMID: 31883967. Presentation: No date and time listed