MMR Status Modulates the Predictive Value of Lymphatic Invasion for Lymph Node Metastasis in Gastric Cancer

Brief Summary Lymph node metastasis (LNM) is a key factor influencing treatment decisions and prognosis in patients with gastric cancer. Lymphatic invasion (LI) is an important pathological predictor of LNM and a core component of the eCURA risk scoring system after endoscopic submucosal dissection (ESD) for early gastric cancer. However, whether LI has the same predictive value for LNM across different mismatch repair (MMR) statuses remains unclear. Compared with proficient mismatch repair (pMMR) gastric cancer, deficient mismatch repair (dMMR) gastric cancer has distinct molecular pathological features and an immune-enriched tumor microenvironment. In early gastric cancer, if LI is associated with a lower LNM risk in dMMR tumors than in pMMR tumors, existing LI-based eCURA risk assessment may overestimate LNM risk in patients with dMMR early gastric cancer and consequently affect decisions regarding additional surgery after ESD. Therefore, this study aims to systematically evaluate the impact of MMR status on the association between LI and LNM using upfront-surgery and post-ESD additional-surgery cohorts from our center, and to explore the potential clinical value of MMR status in refining eCURA-based risk stratification for early gastric cancer.

Inclusion Criteria: 1. Upfront surgery cohort * Patients who underwent radical surgery for gastric cancer at Zhongshan Hospital, Fudan University. * Patients who did not receive neoadjuvant chemotherapy, radiotherapy, immunotherapy, or other antitumor treatments that may affect the pathological assessment of the primary tumor or lymph node metastasis before surgery. * Patients with pathologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma after surgery, including Siewert type II and III tumors only. * Patients with definite pathological assessment of lymphatic invasion and regional lymph node status. * Patients with available and definite MMR status. 2. ESD cohort * Patients who underwent ESD for gastric cancer at Zhongshan Hospital, Fudan University. * Patients with pathologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma after ESD, including Siewert type II and III tumors only. * Patients with complete post-ESD pathological information, including histological type, depth of invasion, tumor size, ulcerative findings, lymphatic invasion status, venous invasion status, horizontal margin status, and vertical margin status. * Patients with available and definite MMR status. Exclusion Criteria: 1. Upfront surgery cohort * Patients with other pathological types, such as gastric squamous cell carcinoma or neuroendocrine carcinoma. * Patients who received neoadjuvant treatment before surgery, including chemotherapy, radiotherapy, immunotherapy, targeted therapy, or other systemic antitumor treatments. * Patients with missing postoperative pathological information, resulting in inability to determine lymphatic invasion or regional lymph node metastasis status. * Patients with missing or indeterminate MMR status. * Patients with concurrent malignancies that may interfere with the determination of the origin of lymph node metastasis. 2. ESD cohort * Patients with other pathological types, such as gastric squamous cell carcinoma or neuroendocrine carcinoma. * Patients with missing post-ESD pathological information that precludes eCURA classification, eCURA risk score calculation, or assessment of lymphatic invasion status. * Patients with missing or indeterminate MMR status.