Anish Thomas1, Yuanbin Chen1, Arlene Berman1, David S Schrump1, Giuseppe Giaccone2, Ira Pastan3, David J Venzon4, David J Liewehr4, Seth M Steinberg4, Markku Miettinen5, Raffit Hassan1, Arun Rajan6. 1. Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. 2. Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA. 3. Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. 4. Biostatistics and Data Management Section, Office of the Clinical Director, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA. 5. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. 6. Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: rajana@mail.nih.gov.
Abstract
OBJECTIVES: Advanced thymic epithelial tumors (TETs) lack adequate treatment options in part due to absence of well characterized tumor-specific antigens. Mesothelin, a cell surface antigen, has been used successfully as a target for tumor-directed therapy. We sought to determine tumor expression and serum levels of mesothelin in patients with TETs. PATIENTS AND METHODS: Tissue samples were obtained from 71 patients with histologically confirmed, unresectable advanced TETs and evaluated for mesothelin expression by immunohistochemistry. The evaluation was blinded for clinical data and outcome. Mesothelin expression and its association with clinico-pathological parameters and survival were assessed. RESULTS: Thymic carcinoma, thymoma, and thymic neuroendocrine tumors (NETs) accounted for 34 (48%), 29 (41%), and 8 (11%) cases respectively. Mesothelin expression was seen in a significantly larger proportion of thymic carcinoma (27/34, 79%) than thymoma (3/29, 10%) (P<0.0001) and was absent in thymic NETs. Among thymic carcinomas 13/34 (38%) showed expression in nearly all tumor cells. Immunoreactivity was membranous, strong, and homogenous. Patients with thymic carcinoma and high mesothelin expression (in >50% of tumor cells) had significantly improved overall survival (median not reached, n=19) compared to patients with no or low mesothelin expression (1.60 years; 95% CI: 1.24-4.94 years; n=15; HR=4.46, 95% CI: 1.55-12.80; p=0.0026). CONCLUSION: Mesothelin expression is frequently observed in advanced thymic carcinomas, infrequently in thymomas and is absent in thymic NETs. Due to strong, membranous expression mesothelin is a potential therapeutic target in thymic carcinoma. Published by Elsevier Ireland Ltd.
OBJECTIVES: Advanced thymic epithelial tumors (TETs) lack adequate treatment options in part due to absence of well characterized tumor-specific antigens. Mesothelin, a cell surface antigen, has been used successfully as a target for tumor-directed therapy. We sought to determine tumor expression and serum levels of mesothelin in patients with TETs. PATIENTS AND METHODS: Tissue samples were obtained from 71 patients with histologically confirmed, unresectable advanced TETs and evaluated for mesothelin expression by immunohistochemistry. The evaluation was blinded for clinical data and outcome. Mesothelin expression and its association with clinico-pathological parameters and survival were assessed. RESULTS:Thymic carcinoma, thymoma, and thymic neuroendocrine tumors (NETs) accounted for 34 (48%), 29 (41%), and 8 (11%) cases respectively. Mesothelin expression was seen in a significantly larger proportion of thymic carcinoma (27/34, 79%) than thymoma (3/29, 10%) (P<0.0001) and was absent in thymic NETs. Among thymic carcinomas 13/34 (38%) showed expression in nearly all tumor cells. Immunoreactivity was membranous, strong, and homogenous. Patients with thymic carcinoma and high mesothelin expression (in >50% of tumor cells) had significantly improved overall survival (median not reached, n=19) compared to patients with no or low mesothelin expression (1.60 years; 95% CI: 1.24-4.94 years; n=15; HR=4.46, 95% CI: 1.55-12.80; p=0.0026). CONCLUSION:Mesothelin expression is frequently observed in advanced thymic carcinomas, infrequently in thymomas and is absent in thymic NETs. Due to strong, membranous expression mesothelin is a potential therapeutic target in thymic carcinoma. Published by Elsevier Ireland Ltd.