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



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.



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.



Serum mesothelin may be a useful noninvasive biomarker surrogate for tumor mesothelin expression in future clinical trials for mesothelin-targeted therapy.
Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan.|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.
Tatsuya
T
Hanaoka
Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan. koseih@saitama-med.ac.jp.|Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan. koseih@saitama-med.ac.jp.
Kosei
K
Hasegawa
Department of Pathology, Saitama Medical University International Medical Center, Saitama, Japan.
Tomomi
T
Kato
Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan.|Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
Sho
S
Sato
Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan.|Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
Akira
A
Kurosaki
Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
Akiko
A
Miyara
Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan.
Shoji
S
Nagao
Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
Hiroyuki
H
Seki
Department of Pathology, Saitama Medical University International Medical Center, Saitama, Japan.
Masanori
M
Yasuda
Department of Gynecologic Oncology, Saitama Medical University International Medical Center, 1397-1 Yamane, Hidaka, Saitama, 350-1298, Japan.|Gynecologic Oncology Translational Research Unit, Project Research Division, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
Keiichi
K
Fujiwara
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood* / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D000090204:Mesothelin; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000378:metabolism* / Q000401:mortality; D011379:Prognosis; D012372:ROC Curve; D012008:Recurrence; D012307:Risk Factors; D047368:Tumor Burden
D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D000090204:Mesothelin