Predictive Patterns of Glutamine Synthetase Immunohistochemical Staining in CTNNB1-mutated Hepatocellular Adenomas

Some hepatocellular adenoma (HCA) subtypes are characterized by different CTNNB1 mutations, leading to beta-catenin activation levels, hence variable immunostaining patterns of glutamine synthetase (GS) expression, and risks malignant transformation. In a retrospective multicentric study 63 resected inflammatory (n=33) noninflammatory (n=30) molecularly confirmed CTNNB1-mutated b-(I)HCA, we investigated the predictive potential 3 known GS as markers for exon 3, 7/8 mutations. Pattern 1 (diffuse homogenous) allowed recognition 17/21 non-S45 mutated b-(I)HCA. 2 heterogenous) identified all b-(I)HCA harboring S45 mutation (20/20). (focal patchy) distinguished 12/22 with both b-HCA b-IHCA showed GS+/CD34? rim diffuse CD34 positivity in center lesion. Interobserver reproducibility was excellent Comparative analysis molecular data 83% 80% sensitivity (b-HCA/b-IHCA) 100% specificity non-S45. For S45, 93% 92% (b-HCA/b-IHCA). 7/8, 55% 96% Preliminary from 16 preoperative needle biopsies same patients suggest that this panel may also be applicable small samples. surgically HCA, distinct can reliably predict which relevant because higher risk The third pattern, although specific, less sensitive identification mutation, but is valuable aid indicate either an or mutation.