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Correlation Between Tumor Mesothelin Expression and Serum Mesothelin in Patients with Epithelial Ovarian Carcinoma: A Potential Noninvasive Biomarker for Mesothelin-targeted Therapy

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Abstract

Background

The cell surface glycoprotein mesothelin is highly expressed in several malignant diseases. Normal mesothelin expression is limited to mesothelial cells lining the pleura, peritoneum, and pericardium, making it a biomarker and an attractive target for cancer therapy.

Methods

We investigated tumor mesothelin expression and serum mesothelin levels in patients with epithelial ovarian cancer or borderline tumors. In total, 161 patients selected from a previous prospective study were analyzed for tumor mesothelin expression using immunohistochemistry and serum mesothelin expression using enzyme-linked immunosorbent assay.

Results

Eighty-eight (68.8%) epithelial ovarian cancers and eight (24.2%) borderline tumors showed high mesothelin expression, which was associated with shorter progression-free and overall survival. The tumor mesothelin expression status was moderately correlated with serum mesothelin levels in epithelial ovarian cancer patients. Based on receiver operating characteristic analysis, a serum mesothelin level above 2.20 nM predicted high tumor mesothelin expression in epithelial ovarian cancer patients (area under the curve = 0.81). In 45 patients with recurrent epithelial ovarian cancer, we observed relatively lower levels of serum mesothelin, compared to the level at the primary diagnosis. We also tracked the change in the serum mesothelin level during the course of second-line chemotherapy and found a discrepancy between the clinical response and the serum mesothelin change in some patients, which suggested tumor heterogeneity among the tumor cells with or without mesothelin expression.

Conclusion

Serum mesothelin may be a useful noninvasive biomarker surrogate for tumor mesothelin expression in future clinical trials for mesothelin-targeted therapy.

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Acknowledgements

We thank Dr. N. Iwasa and Dr. T. Nishikawa for their helpful support in sample collection during our study.

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Authors and Affiliations

  1. Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan

    Tatsuya Hanaoka, Kosei Hasegawa, Sho Sato, Akira Kurosaki, Shoji Nagao & Keiichi Fujiwara

  2. Department of Pathology, Saitama Medical University International Medical Center, Saitama, Japan

    Tomomi Kato & Masanori Yasuda

  3. Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan

    Tatsuya Hanaoka, Kosei Hasegawa, Sho Sato, Akira Kurosaki, Akiko Miyara & Keiichi Fujiwara

  4. Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, Saitama, Japan

    Tatsuya Hanaoka & Hiroyuki Seki

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  1. Tatsuya Hanaoka
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  2. Kosei Hasegawa
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  3. Tomomi Kato
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Correspondence to Kosei Hasegawa.

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Conflict of interest

Authors Hanaoka, Hasegawa, Kato, Sato, Kurosaki, Miyara, Nagao, Seki, Yasuda, and Fujiwara declare that they have no conflict of interest.

Funding

This study was partially supported by a grant from Hidaka Research Projects at Saitama Medical University International Medical Center (Saitama, Japan), a Saitama Medical University Internal Research Grant, and a grant from the Ochiai Memorial Award 2012.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Informed consent was obtained from all individual participants included in the study.

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40291_2017_255_MOESM3_ESM.docx

Supplementary material 3 (DOCX 115 kb) Fig. 1 Kaplan–Meier survival curves in ovarian cancer patients, based on the serum mesothelin level (a and c) and on CA125 level (b and d). Statistical analysis of prognostic survival was performed using the log-rank test. OS overall survival, PFS progression-free survival

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Hanaoka, T., Hasegawa, K., Kato, T. et al. Correlation Between Tumor Mesothelin Expression and Serum Mesothelin in Patients with Epithelial Ovarian Carcinoma: A Potential Noninvasive Biomarker for Mesothelin-targeted Therapy. Mol Diagn Ther 21, 187–198 (2017). https://doi.org/10.1007/s40291-017-0255-2

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