Cancer antigen profiling for malignant pleural mesothelioma immunotherapy: expression and coexpression of mesothelin, cancer antigen 125, and Wilms tumor 1
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Takashi Eguchi1,2, Kyuichi Kadota1,3,4, Marissa Mayor1, Marjorie G. Zauderer5, Andreas Rimner6, Valerie W. Rusch1, William D. Travis3, Michel Sadelain7 and Prasad S. Adusumilli1,7
1Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
2Division of Thoracic Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan
3Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
4Department of Diagnostic Pathology, Faculty of Medicine, Kagawa University, Kagawa, Japan
5Thoracic Oncology Service, Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
6Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
7Center for Cell Engineering, Memorial Sloan Kettering Cancer Center, New York, NY, USA
Prasad S. Adusumilli, email: firstname.lastname@example.org
Keywords: mesothelin, CA125, WT1, mesothelioma, chimeric antigen receptor
Received: May 10, 2017 Accepted: August 15, 2017 Published: September 12, 2017
Background: To develop cancer antigen-targeted immunotherapeutic strategies for malignant pleural mesothelioma (MPM), we investigated the individual and coexpressions of the cancer-associated antigens mesothelin (MSLN), cancer antigen 125 (CA125), and Wilms tumor 1 (WT1) in both epithelioid and non-epithelioid MPM.
Methods: All available hematoxylin and eosin-stained slides from patients who were diagnosed with MPM (1989-2010) were reviewed. We constructed tissue microarrays from 283 patients (epithelioid = 234; non-epithelioid = 49). Intensity and distribution for each antigen were assessed by immunohistochemistry.
Results: Positive expression of MSLN, CA125, and WT1 were demonstrated in 93%, 75%, and 97% of epithelioid MPM cases, and 57%, 33%, and 98% of non-epithelioid MPM cases, respectively. Triple- and double-positive antigen coexpressions were demonstrated in 72% and 23% of epithelioid MPM cases and 29% and 33% of non-epithelioid MPM cases, respectively. Complete absence of expression for all three antigens was demonstrated in <2% of MPM cases. More than two-thirds of MPM cases had ≥50% distribution of MSLN-positive cells and, among the remaining third, half had ≥50% distribution of WT1-positive cells. CA125/MSLN coexpression was observed in more than two-thirds of epithelioid MPM cases and one-third of non-epithelioid MPM cases.
Conclusion: A limited number of cancer-associated antigens can target almost all MPM tumors for immunotherapy.
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