Biology of Mesothelin and Clinical Implications: A Review of Existing Literature

Our plain-English summary of Biology of Mesothelin and Clinical Implications: A Review of Existing Literature, by B.L. Hagerty, K. Takabe (World Journal of Oncology, 2023).

The study

• Authors: B.L. Hagerty, K. Takabe
• Journal: World Journal of Oncology
• Published: 2023;14(5):340-349
• Type of article: Review
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Since its discovery in 1992, mesothelin (MSLN) has generated significant interest as a therapeutic target. A number of characteristics make it ideal for this purpose. First, it is not expressed on the parenchyma of any vital organs. Second, it is differentially expressed on a number of cancer types that have relatively poor prognosis and lack effective systemic options. Third, it is expressed on the cell membrane making it accessible to large molecule targeted therapies. However, unlike other drug targets that have been exploited for therapeutic benefit, the precise function of MSLN, why it is expressed in certain cancers, and its biological role have not been clearly elucidated. Here the existing literature on the cellular function and expression patterns of MSLN across tumor types is reviewed in order to gain further understanding of this intriguing molecule. In doing so, we conclude that there remains significant ambiguity surrounding its function and role in cellular and tumor biology. Furthermore, the expression of MSLN and its relation of prognosis seems to depend on the type of tumor. Finally, the unified mechanism by which MSLN acts as a protein that conveys tumor aggressiveness remains elusive. What is clear is that there is much yet to be discovered in this realm and doing so may have large implications for treatment of otherwise lethal malignancies.

Copyright 2023, Hagerty et al.

In plain English

This article was a narrative review, not a new study, and it did not study asbestos exposure. The authors reviewed published research on mesothelin, a protein found on the linings of the chest, heart and abdomen (pleura, pericardium and peritoneum) and on several cancers. Pooling earlier staining studies in a table, the authors counted mesothelin in 150/163 (92.0%) epithelioid mesotheliomas, 617/655 (94.2%) non-mucinous epithelial ovarian cancers, 267/298 (89.6%) pancreatic adenocarcinomas, 920/1,878 (49.0%) gastric adenocarcinomas and 178/449 (39.6%) triple negative breast cancers. In one cited study, 0/8 sarcomatoid mesotheliomas stained positive. From the cited mesothelioma studies, the authors wrote that loss of mesothelin in the tumor was associated with worse overall survival. They suggested that blood levels of mesothelin-related protein likely reflect tumor burden. They noted that the blood marker is listed in NCCN guidelines for pleural and peritoneal mesothelioma. The authors concluded that how mesothelin relates to prognosis seems to depend on tumor type and that its function remains unclear. They noted that laboratory staining methods differed between studies.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative literature review (no new patients or experiments)
• Who was studied: Published studies on mesothelin in normal tissue and in tumors, including epithelioid mesothelioma, epithelial ovarian cancer, pancreatic adenocarcinoma, gastric adenocarcinoma and triple negative breast cancer; no search method or study count given
• Exposure: Not an asbestos exposure study; the subject was expression of the protein mesothelin (MSLN) in tissues and tumors
• Main results:
  • Pooled across cited staining studies, 150/163 (92.0%) epithelioid mesotheliomas were mesothelin positive
  • Pooled, 617/655 (94.2%) non-mucinous epithelial ovarian cancers were mesothelin positive
  • Pooled, 267/298 (89.6%) pancreatic adenocarcinomas were mesothelin positive
  • Pooled, 920/1,878 (49.0%) gastric adenocarcinomas were mesothelin positive
  • Pooled, 178/449 (39.6%) triple negative breast cancers were mesothelin positive
  • In a cited study using the 5B2 antibody, 0/8 sarcomatoid mesothelioma tissues stained positive
  • From the cited mesothelioma studies, the authors wrote that loss of mesothelin in the tumor was associated with worse overall survival
  • The authors suggested that blood levels of mesothelin-related proteins likely reflect tumor burden
  • The authors noted that the soluble mesothelin blood marker is listed in NCCN guidelines for pleural and peritoneal mesothelioma
• The authors' conclusion: The authors concluded that the link between mesothelin and prognosis seems to depend on the type of tumor, and that its function and mechanism remain unclear
• Limitations the authors state:
  • The authors noted that the evidence they reviewed was hard to compare: staining (IHC) methods differed between institutions, and sensitivity depended on the antibody used

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Discovery, Parenchyma, Prognosis.

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