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Updated: Sep 29, 2025
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Published on: October 2, 2015
Interpatient variability in mesothelin expression necessitates its evaluation before gastric cancer immunotherapy
Masoud Sotoudeh1, Vahid Mansouri2, Ramin Shakeri3
1Digestive Diseases Research Center, Digestive Disease Research Institute, Tehran University of Medical Sciences, Tehran, Iran.
Abstract:
Aims: Mesothelin (MSLN) was applied for the immunotherapy of ovarian cancer and mesothelioma with a minimum expression of 60% to obtain a clinical response. Here, the authors evaluated MSLN expression as a potential target of gastric adenocarcinoma immunotherapy. Materials & methods: The expression of MSLN was evaluated by immunohistochemistry and was reported in primary tumor (PT) and metastatic tumor (MT) sites. Results: The results showed that only 17.1% and 13.5% of the patients had 60% or more MSLN expression in PT and MT sites, respectively. The expression of MSLN in PTs and MTs was not influenced by Lauren classification, neoadjuvant therapy or tumor stage. Conclusions: Interpatient variability in MSLN expression necessitates its evaluation before MSLN-based gastric cancer immunotherapy.
Insights
Mesothelin (MSLN) shows low expression in most gastric cancers, limiting its use in immunotherapy. Individual patient MSLN levels must be assessed before considering MSLN-targeted gastric cancer treatments.
Area of Science:
- Oncology
- Immunotherapy
- Gastroenterology
Background:
- Mesothelin (MSLN) is a promising target for cancer immunotherapy, particularly in ovarian cancer and mesothelioma.
- A minimum MSLN expression of 60% is typically required for effective immunotherapy response.
- The potential of MSLN as a therapeutic target in gastric adenocarcinoma remains to be fully elucidated.
Purpose of the Study:
- To evaluate the expression levels of mesothelin (MSLN) in gastric adenocarcinoma.
- To determine the suitability of MSLN as a target for immunotherapy in gastric cancer patients.
Main Methods:
- Immunohistochemistry was used to assess MSLN expression.
- MSLN expression was quantified in both primary tumor (PT) and metastatic tumor (MT) tissues.
- Expression data were analyzed in relation to Lauren classification, neoadjuvant therapy, and tumor stage.
Main Results:
- Only 17.1% of primary tumors and 13.5% of metastatic tumors exhibited MSLN expression at or above the 60% threshold.
- MSLN expression levels in PTs and MTs were not significantly correlated with Lauren classification, neoadjuvant therapy, or tumor stage.
- Significant interpatient variability in MSLN expression was observed.
Conclusions:
- The low and variable expression of MSLN in gastric adenocarcinoma suggests limitations for its broad application in MSLN-based immunotherapy.
- Pre-treatment evaluation of individual MSLN expression levels is crucial before initiating MSLN-targeted gastric cancer immunotherapy.
- Further research may be needed to identify patient subgroups who could benefit from MSLN-targeted therapies.
