GLP-1 receptor expression in a molecularly characterized cohort of endometrial carcinoma: Results from the GEICO 163-T/SPECTRUM study.

5625 Background: The glucagon-like peptide-1 receptor (GLP-1R) plays a central role in metabolic, and hormonal signaling and has gained increasing clinical relevance due to the widespread use of GLP-1R agonists. Given the strong link between obesity and endometrial carcinoma (EC), data on GLP-1R expression in EC are of clinical interest. We aimed to evaluate GLP-1R expression in a large, molecularly classified EC cohort and analyze its association with clinicopathological and molecular features. Methods: GLP-1R immunohistochemistry was performed on tissue microarrays from 192 ECs included in the SPECTRUM cohort. This cohort included 111 low grade endometrioid and 81 high grade ECs. 187 tumors were successfully classified according to WHO 2020 criteria, including 3% POLE-mutated (POLEmut), 25% mismatch repair–deficient (dMMR), 43% no specific molecular profile (NSMP), and 29% p53 abnormal (p53abn) carcinomas. Additionally, CTNNB1 mutation status was available in 168 tumors (16% mutated). GLP-1R expression was evaluated using the Allred scoring system (range 0–8). GLP-1R positivity was defined as Allred ≥6 according to previously published criteria (Kanda et al. 2018). Associations were evaluated using univariable analyses and multivariable logistic regression, reporting ORs with 95% confidence intervals; p