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

NCT07625735 | Not Yet Recruiting

• 1 other identifier: ZSGC
• Study Type: observational
• Target: 3,000
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Mismatch Repair Deficient or MSI-High Solid Tumors; Gastric / Gastroesophageal Junction Adenocarcinoma; Lymph Node Metastasis; Lymphatic Invasion

Outcome Measures

Primary Outcomes (1)

• Lymph Node Metastasis Rate Among LI-Positive Gastric Cancer Patients

  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.

  At postoperative pathological assessment, approximately 14 days after upfront surgery

Secondary Outcomes (4)

• LI Positivity Rate According to MMR Status

  At postoperative pathological assessment, approximately 14 days after upfront surgery

• Overall LNM Rate According to MMR Status

  At postoperative pathological assessment, approximately 14 days after upfront surgery

• eCURA Risk Stratification and LI Contribution in the Gastric Cancer ESD Cohort

  At pathological assessment of the ESD specimen, approximately 14 days after ESD

• LNM Rate Among LI-Positive Patients in the cohort undergoing additional gastrectomy after ESD

  At postoperative pathological assessment, approximately 14 days after additional surgery

Study Arms (2)

dMMR gastric cancer

Patients with gastric cancer classified as deficient mismatch repair (dMMR) based on routine pathological testing.

Other: Mismatch repair (MMR) status; Other: Lymphatic invasion status

pMMR gastric cancer

Patients with gastric cancer classified as proficient mismatch repair (pMMR) based on routine pathological assessment.

Other: Mismatch repair (MMR) status; Other: Lymphatic invasion status

Interventions

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.

dMMR gastric cancer; pMMR gastric cancer

Lymphatic invasion status OTHER

Lymphatic invasion status was determined from routine pathological reports and classified as LI-positive or LI-negative.

dMMR gastric cancer; pMMR gastric cancer

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with pathologically confirmed gastric adenocarcinoma or gastroesophageal junction adenocarcinoma treated at Zhongshan Hospital, Fudan University. The study population includes two retrospective cohorts: patients who underwent upfront radical surgery between January 2018 and April 2026, and patients who underwent endoscopic submucosal dissection (ESD) between January 2021 and March 2026 with available mismatch repair (MMR) status. Patients are classified according to MMR status as deficient mismatch repair (dMMR) or proficient mismatch repair (pMMR).

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Shanghai Zhongshan Hospital: lead

MeSH Terms

Conditions

Turcot syndrome; Lymphatic Metastasis

Interventions

DNA Mismatch Repair

Condition Hierarchy (Ancestors)

Neoplasm Metastasis; Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

DNA Repair; Biochemical Phenomena; Chemical Phenomena; Genetic Phenomena

Central Study Contacts

Zhaoqing Tang

CONTACT

86-021-64041990; tang.zhaoqing@zs-hospital.sh.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2026
• First Posted: June 4, 2026
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): July 31, 2027
• Last Updated: June 4, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share