title: Expression of mesothelin in thymic carcinoma and its potential therapeutic significance.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors: Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Anish
authors: A
authors: Thomas
authors: Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Yuanbin
authors: Y
authors: Chen
authors: Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Arlene
authors: A
authors: Berman
authors: Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: David S
authors: DS
authors: Schrump
authors: Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC 20007, USA.
authors: Giuseppe
authors: G
authors: Giaccone
authors: Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Ira
authors: I
authors: Pastan
authors: 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.
authors: David J
authors: DJ
authors: Venzon
authors: 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.
authors: David J
authors: DJ
authors: Liewehr
authors: 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.
authors: Seth M
authors: SM
authors: Steinberg
authors: Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Markku
authors: M
authors: Miettinen
authors: Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
authors: Raffit
authors: R
authors: Hassan
authors: Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: rajana@mail.nih.gov.
authors: Arun
authors: A
authors: Rajan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood / Q000378:metabolism*; D006801:Humans; D008297:Male; D008479:Mediastinal Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D000090204:Mesothelin; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000145:classification* / Q000473:pathology; D015995:Prevalence; D013534:Survival; D013945:Thymoma / Q000453:epidemiology / Q000208:ethnology / Q000378:metabolism* / Q000473:pathology; D013953:Thymus Neoplasms / Q000145:classification* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D000090204:Mesothelin
keywords: Immunohistochemistry; Immunotherapy; Mesothelin; Therapeutic target; Thymic carcinoma