ИСТИНА

Background & Objectives: Heterogeneity in mismatch repair (MMR) protein expression between primary tumors and metastases remains understudied in gastric cancer (GC). We aimed to assess the prevalence of heterogeneous MMR status (hMMR) in lymph node metastases of GC and explore its associations with clinicopathological features to inform prognosis and therapy. Methods: We analyzed 33 GC patients with confirmed lymph node metastases and no prior neoadjuvant therapy. Full-sized surgical specimens were evaluated immunohistochemically using antibodies against MSH2 (79H11), MSH6 (EP49), MLH1 (ES05), and PMS2 (EP51). hMMR was defined as uneven staining (≥20% variability) of any marker in primary tumors or metastases. We correlated hMMR in metastases with sex, age, tumor site, macroscopic type, size, histologic subtype, differentiation, vascular emboli, TNM stage, and clinical stage. Statistical significance was assessed using χ2 or Fisher’s exact tests in Statistica 12.5.192.7, with p<0.05 considered significant. Results: hMMR in lymph node metastases occurred in 5/33 cases (15.2%): three showed hMMR in both primary tumor and metastases, while two had stable primary tumor staining but hMMR in metastases. One additional case revealed microsatellite instability (MSI) exclusively in metastases, not the primary tumor. The mucinous subtype was significantly enriched in the hMMR-metastases group (p=0.024), contrasting with the intestinal subtype dominating the stable-MMR group. hMMR in metastases strongly correlated with advanced N stages (N3, p<0.001) compared to stable MMR (N1-2). No associations with sex, age, or tumor size were observed. Conclusion: Heterogeneous MMR status in GC lymph node metastases, though uncommon (15.2%), is linked to mucinous histology and advanced nodal spread. This suggests clonal evolution with potential implications for prognosis and immunotherapy responsiveness.