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

May 29, 2026 updated by: Shanghai Zhongshan Hospital

Mismatch Repair (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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Observational

Enrollment (Estimated)

3000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

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).

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
dMMR gastric cancer
Patients with gastric cancer classified as deficient mismatch repair (dMMR) based on routine pathological testing.
Other: Mismatch repair (MMR) status
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.
Other: Lymphatic invasion status
Lymphatic invasion status was determined from routine pathological reports and classified as LI-positive or LI-negative.
pMMR gastric cancer
Patients with gastric cancer classified as proficient mismatch repair (pMMR) based on routine pathological assessment.
Other: Mismatch repair (MMR) status
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.
Other: Lymphatic invasion status
Lymphatic invasion status was determined from routine pathological reports and classified as LI-positive or LI-negative.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Lymph Node Metastasis Rate Among LI-Positive Gastric Cancer Patients
Time Frame: 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.
At postoperative pathological assessment, approximately 14 days after upfront surgery

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LI Positivity Rate According to MMR Status
Time Frame: 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.
At postoperative pathological assessment, approximately 14 days after upfront surgery
Overall LNM Rate According to MMR Status
Time Frame: 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.
At postoperative pathological assessment, approximately 14 days after upfront surgery
eCURA Risk Stratification and LI Contribution in the Gastric Cancer ESD Cohort
Time Frame: 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.
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
Time Frame: 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.
At postoperative pathological assessment, approximately 14 days after additional surgery

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Shanghai Zhongshan Hospital

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2026

Primary Completion (Estimated)

November 30, 2026

Study Completion (Estimated)

July 31, 2027

Study Registration Dates

First Submitted

May 19, 2026

First Submitted That Met QC Criteria

May 29, 2026

First Posted (Actual)

June 4, 2026

Study Record Updates

Last Update Posted (Actual)

June 4, 2026

Last Update Submitted That Met QC Criteria

May 29, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZSGC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Individual participant data will not be publicly shared due to patient privacy concerns and institutional data protection regulations. De-identified aggregate data may be made available from the corresponding author upon reasonable request and with appropriate institutional approval.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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