The Role of Mesothelin Expression in Serous Ovarian Carcinoma: Impacts on Diagnosis, Prognosis, and Therapeutic Targets

Our plain-English summary of The Role of Mesothelin Expression in Serous Ovarian Carcinoma: Impacts on Diagnosis, Prognosis, and Therapeutic Targets, by G. Giordano, E. Ferioli, A. Tafuni (Cancers, 2022).

The study

• Authors: G. Giordano, E. Ferioli, A. Tafuni
• Journal: Cancers
• Published: 2022;14(9)
• Type of article: Review
• Cited by: 19 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mesothelin (MSLN) is a protein expressed in the mesothelial cell lining of the pleura, peritoneum, and pericardium; its biological functions in normal cells are still unknown. Experimental studies using knockout mice have suggested that this molecule does not play an important role in development and reproduction. In contrast, it has been observed that this molecule is produced in abnormal amounts in several malignant neoplasms, such as mesotheliomas and pancreatic adenocarcinomas. Many molecular studies have also demonstrated that mesothelin is overexpressed in HSOCs. Here, we discuss the current knowledge of mesothelin and focus on its role in clinical and pathological diagnoses, as well as its impact on the prognosis of HSOC. Moreover, regarding the binding of MSLN to the ovarian cancer antigen CA125, which has been demonstrated in many studies, we also report on signal transduction pathways that may play an important role in the spread and neoplastic progression of this lethal neoplasm. Given that mesothelin is overexpressed in many solid tumours and has antigenic properties, this molecule could be considered an antigenic target for the treatment of many malignancies. Consequently, we also review the literature to report on mesothelin-targeting therapies for HSOC that have been recently investigated in many clinical studies.

In plain English

This article was a review, not an original study. Its three authors, from the Pathology Unit at the University of Parma, Italy, discussed published research on mesothelin in high-grade serous ovarian carcinoma. Mesothelin is a protein found in the lining of the chest and abdominal cavities and produced in some cancers, including mesotheliomas. The article did not study asbestos exposure. The authors described studies reporting that blood levels of a soluble form of mesothelin were higher in women with this ovarian cancer. They called the evidence on mesothelin and outlook limited and conflicting. One study of 42 advanced cases linked high mesothelin to a poor prognosis. Another, of 105 advanced cases, linked diffuse mesothelin to longer survival. A third, of 107 cases, found it did not predict outcome. The authors also reviewed early clinical trials of mesothelin-targeting treatments, some of which were terminated. They concluded that the literature suggests mesothelin can be used as a diagnostic marker for this cancer and is a promising treatment target, and that further studies are needed.

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
• Who was studied: Published studies and clinical trials on mesothelin in ovarian carcinoma, mainly high-grade serous ovarian carcinoma (HSOC). These included six tabulated prognostic studies, with case numbers from 14 to 386, and nine listed clinical trials of mesothelin-targeting therapies. The authors also showed one illustrative case of their own: a woman with a BRCA-1 mutation who had a serous tubal intraepithelial carcinoma (STIC) and a small invasive serous carcinoma.
• Exposure: No asbestos or fiber exposure was studied. The review concerns expression of the protein mesothelin (MSLN) in tumours and body fluids, its binding to CA125, and treatments that target mesothelin.
• Main results:
  • The authors reported that published immunohistochemical data on mesothelin expression and prognosis in ovarian cancers were limited and conflicting.
  • In a reviewed study by Yildiz et al. (42 advanced-stage HSOC cases), high mesothelin expression in advanced serous ovarian cancers was associated with a poor prognosis and worse platinum sensitivity.
  • In a reviewed study by Yen et al. (105 advanced-stage HSOC cases), diffuse mesothelin expression was correlated with prolonged survival of HSOC patients.
  • In a reviewed study by Magalhaes et al. (107 cases), mesothelin expression in patients with advanced serous carcinomas did not predict clinical outcome.
  • A reviewed patient-derived xenograft study reported that free CA125 promoted ovarian cancer cell migration and tumour metastasis by binding with mesothelin.
  • In a phase I trial of the anti-mesothelin immunotoxin SS1P (NCT00066651), patients with ovarian carcinomas had stable disease. Side effects included capillary leak syndrome and pleuritis, attributed to SS1P binding to normal mesothelial cells.
  • Among the listed trials, the CRS-207 combination trial in platinum-resistant ovarian, fallopian or serous peritoneal cancer (NCT02575807) was terminated for low enrollment and lack of clinical activity.
  • In the authors' single illustrative case, both the STIC and the small invasive serous carcinoma showed marked mesothelin positivity on immunohistochemistry.
• The authors' conclusion: The authors concluded that the literature suggests mesothelin can be used as a marker for the clinical and pathological diagnosis of high-grade serous ovarian carcinoma and is a promising therapeutic target. They added that further studies would be useful.
• Limitations the authors state:
  • The authors stated that the conflicting prognostic findings may be due to the different antibodies, protocols and criteria the studies used to evaluate immunoreactivity.
  • The authors found no immunohistochemical studies relating the pattern of mesothelin expression to prognosis in HSOC.
  • The authors found no studies evaluating mesothelin expression in STIC or in HSOC arising from it.

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Carcinoma, Prognosis, Mesothelial Cells, Pleura, Peritoneum, Pericardium, Neoplasm.

Related studies

• Cytokeratin 5/6 expression, prognosis, and association with estrogen receptor α in high-grade serous ovarian carcinoma — E.T. Taube, C. Denkert, et al. (2017)
• PAX8 Expression in a Subset of Malignant Peritoneal Mesotheliomas and Benign Mesothelium has Diagnostic Implications in the Differential Diagnosis of Ovarian Serous Carcinoma — D.B. Chapel, A.N. Husain, et al. (2017)
• Evaluation of MTAP immunohistochemistry loss of expression in ovarian serous borderline tumors as a potential marker for prognosis and progression — N. Nilforoushan, N.A. Moatamed (2020)
• Expression of the Ets transcription factor EHF in serous ovarian carcinoma effusions is a marker of poor survival — K. Brenne, D.A. Nymoen, et al. (2012)
• Aquaporins 1, 3 and 5 in Different Tumors, their Expression, Prognosis Value and Role as New Therapeutic Targets — M.S. Moosavi, Y. Elham (2020)
• Clinical significance of 9P21 gene combined with BAP1 and MTAP protein expression in diagnosis and prognosis of mesothelioma serous effusion — G.Y. Ma, S. Shi, et al. (2022)

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