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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| dMMR gastric cancer | Patients with gastric cancer classified as deficient mismatch repair (dMMR) based on routine pathological testing. |
| |
| pMMR gastric cancer | Patients with gastric cancer classified as proficient mismatch repair (pMMR) based on routine pathological assessment. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| LI Positivity Rate According to MMR Status | 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 |
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Inclusion Criteria:
Upfront surgery cohort
ESD cohort
Exclusion Criteria:
Upfront surgery cohort
ESD cohort
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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).
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Zhaoqing Tang | Contact | 86-021-64041990 | tang.zhaoqing@zs-hospital.sh.cn |
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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.
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| Lymphatic invasion status | Other | Lymphatic invasion status was determined from routine pathological reports and classified as LI-positive or LI-negative. |
|
| Overall LNM Rate According to MMR Status | 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 | 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 | 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 |
| ID | Term |
|---|---|
| C536928 | Turcot syndrome |
| D008207 | Lymphatic Metastasis |
| ID | Term |
|---|---|
| D009362 | Neoplasm Metastasis |
| D009385 | Neoplastic Processes |
| D009369 | Neoplasms |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D053843 | DNA Mismatch Repair |
| ID | Term |
|---|---|
| D004260 | DNA Repair |
| D001669 | Biochemical Phenomena |
| D055598 | Chemical Phenomena |
| D055614 | Genetic Phenomena |
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