Endocrine Abstracts

JOINT590

Background: Although surgery is widely accepted as the first-line treatment for acromegaly, its success rate remains variable. Pharmacologic therapy with first-generation somatostatin receptor ligands (fgSRLs) is frequently employed for patients with persistent acromegaly after surgery. However, resistance to these agents is common, highlighting the need for biomarkers that predict treatment response. We aimed to analyze the roles of known immunohistochemical (IHC) biomarkers and a novel marker, the cytoskeleton protein Filamin A (FLNA), in predicting treatment response and their associations with tumor characteristics.

Materials and Methods: We conducted an IHC study to evaluate the expression of somatostatin receptor subtypes (SSTR2 and SSTR5), cytokeratin granulation patterns (densely vs sparsely granulated), E-Cadherin, and FLNA in tissue samples from acromegaly patients who underwent surgery. Paraffin-embedded tumor samples were analyzed, and clinical data were retrospectively collected from patient files. This included information on surgical outcomes, pharmacological treatment response, and imaging data regarding tumor size and invasiveness.

Results: 30 patients were included, with fgSRL treatment response data available for 21 patients. Resistance to fgSRLs was more frequently observed in patients with sparsely granulated tumors and lower IHC expression of SSTR2 and E-Cadherin. Positive correlations were identified between IGF-1 decrease after six months of fgSRL treatment and the expression of SSTR2 (P = 0.024, r = 0.49) and E-Cadherin (P = 0.009, r = 0.64). No correlation was found for SSTR5 expression. ROC curve analysis identified E-Cadherin as the best predictor of fgSRL response, achieving 100% sensitivity and specificity, surpassing SSTR2 and granulation patterns. FLNA expression was positive in all tumor samples, and higher FLNA expression was significantly associated with SSTR5 expression and suprasellar invasion.

Conclusions: IHC analysis of SSTR2 and E-Cadherin provides valuable insights for predicting fgSRL treatment responses in acromegaly. Densely granulated tumors with positive SSTR2 and E-Cadherin expression are associated with favorable outcomes, with E-Cadherin emerging as the most reliable predictive marker. The associations we observed between FLNA and SSTR5, as well as FLNA and tumor invasiveness warrant further investigation to clarify the predictive and prognostic role of FLNA in pituitary tumors. Incorporating IHC evaluation of these biomarkers in clinical practice may enable a more personalized therapeutic approach for patients with acromegaly.

Keyword(s): pituitary, acromegaly, Immunohistochemistry, Filamin A, biomarkers.