High Frequency of RhoGAP Fusion and Muscularis Mucosae Invasion in pT1a Gastric Adenocarcinoma Harboring Lymph Node Metastasis

ABSTRACT Gastric cancer (GC) confined to the mucosa (pT1a‐GC) has a low incidence (approximately 3%) of lymph node metastasis (LNM), making it a suitable candidate for endoscopic resection. However, the current risk stratification system inadequately identifies high‐risk patients. Although RhoGAP fusion has been identified as a risk factor for LNM in pT1b‐GC, its role in pT1a‐GC remains unclear. In the present study, medical records of 1099 surgically resected pT1a‐GC cases over 12 years were reviewed, identifying 33 cases (3.0%) with LNM. A case‐control study compared these cases to 99 LNM‐negative cases based on clinicopathological data. Histological reviews and fluorescence In Situ hybridization assays to evaluate RhoGAP fusions, represented by CLDN18 :: ARHGAP26 , were conducted. Univariate analysis revealed significant associations between LNM and larger tumor size (> 30 mm), mixed histological type, muscularis mucosae invasion (MMI), microtubular‐mucocellular histology, and RhoGAP fusion. Multivariate analysis identified RhoGAP fusion and MMI as independent LNM predictors. Among LNM‐positive cases, RhoGAP fusion was observed in 51.5% (17/33) and was associated with younger age and less frequent MMI. In conclusion, RhoGAP fusion and MMI may be significant biomarkers for LNM in pT1a‐GC. Incorporating these factors could enhance risk stratification and inform clinical management strategies for pT1a‐GC.