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

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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.

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