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

• Mismatch repair (MMR) status (Other): Mismatch repair (MMR) status was assessed as part of routine pathological evaluation. Patients were classified as deficient mismatch repair (dMMR) or proficient mismatch repair (pMMR) according to immunohistochemical expression of MLH1, PMS2, MSH2, and MSH6.
• Lymphatic invasion status (Other): Lymphatic invasion status was determined from routine pathological reports and classified as LI-positive or LI-negative.

Primary outcomes

• Lymph Node Metastasis Rate Among LI-Positive Gastric Cancer Patients [At postoperative pathological assessment, approximately 14 days after upfront surgery]: LI positivity is defined as lymphatic invasion explicitly documented in the pathological report or tumor emboli within lymphatic vessels confirmed by D2-40 immunohistochemistry. LNM is defined as regional lymph node metastasis confirmed by postoperative pathological examination. The LNM rate among LI-positive patients is calculated as the number of patients with LNM divided by the total number of LI-positive patients in the corresponding group.

Secondary outcomes

• LI Positivity Rate According to MMR Status [At postoperative pathological assessment, approximately 14 days after upfront surgery]: This outcome evaluates differences in LI positivity rate between patients with dMMR and pMMR gastric cancer. LI positivity rate is calculated as the number of LI-positive patients divided by the total number of patients in each MMR group.
• Overall LNM Rate According to MMR Status [At postoperative pathological assessment, approximately 14 days after upfront surgery]: This outcome evaluates differences in overall LNM rate between patients with dMMR and pMMR gastric cancer. Overall LNM rate is calculated as the number of patients with pathologically confirmed LNM divided by the total number of patients in each MMR group.
• eCURA Risk Stratification and LI Contribution in the Gastric Cancer ESD Cohort [At pathological assessment of the ESD specimen, approximately 14 days after ESD]: This outcome evaluates differences in eCURA classification, eCURA risk score distribution, and the contribution of LI to the risk score between dMMR and pMMR patients in the gastric cancer ESD cohort. LI contribution is assessed based on its role in eCURA-C2 classification and/or its component score contribution within the eCURA risk scoring system.
• LNM Rate Among LI-Positive Patients in the cohort undergoing additional gastrectomy after ESD [At postoperative pathological assessment, approximately 14 days after additional surgery]: This outcome evaluates differences in LNM risk between LI-positive dMMR and pMMR patients with early gastric cancer who underwent additional surgery after ESD. LNM is defined as regional lymph node metastasis confirmed by pathological examination of the additional surgical specimen. LNM rate is calculated as the number of patients with LNM divided by the total number of LI-positive patients in each MMR group.

Sex: All, ages: 18 Years to 95 Years

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.