Correlation Between Tumor Mesothelin Expression and Serum Mesothelin in Patients with Epithelial Ovarian Carcinoma: A Po
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ORIGINAL RESEARCH ARTICLE
Correlation Between Tumor Mesothelin Expression and Serum Mesothelin in Patients with Epithelial Ovarian Carcinoma: A Potential Noninvasive Biomarker for Mesothelin-targeted Therapy Tatsuya Hanaoka1,3,4 • Kosei Hasegawa1,3 • Tomomi Kato2 • Sho Sato1,3 Akira Kurosaki1,3 • Akiko Miyara3 • Shoji Nagao1 • Hiroyuki Seki4 • Masanori Yasuda2 • Keiichi Fujiwara1,3
•
Ó Springer International Publishing Switzerland 2017
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 enzymelinked 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.
Key Points Electronic supplementary material The online version of this article (doi:10.1007/s40291-017-0255-2) contains supplementary material, which is available to authorized users. & Kosei Hasegawa [email protected] 1
Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan
2
Department of Pathology, Saitama Medical University International Medical Center, Saitama, Japan
3
4
Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, Saitama, Japan
Serum mesothelin levels are correlated with tumor mesothelin expr
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