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Expression of mesothelin in thymic carcinoma and its potential therapeutic significance

Anish Thomas1, Yuanbin Chen1, Arlene Berman1

  • 1Thoracic and Gastrointestinal Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Lung Cancer (Amsterdam, Netherlands)
|October 31, 2016
PubMed
Abstract

Insights

Mesothelin is frequently expressed in advanced thymic carcinomas, making it a potential therapeutic target. High expression in thymic carcinoma correlates with improved survival, unlike in thymomas or thymic neuroendocrine tumors.

Area of Science:

  • Oncology
  • Immunology
  • Biomarker Research

Background:

  • Advanced thymic epithelial tumors (TETs) have limited treatment options due to a lack of well-defined tumor-specific antigens.
  • Mesothelin, a cell surface antigen, has demonstrated success as a target in other tumor-directed therapies.
  • Investigating mesothelin expression in TETs is crucial for identifying potential therapeutic targets.

Purpose of the Study:

  • To determine the expression levels of mesothelin in tumor tissues and serum of patients with advanced thymic epithelial tumors (TETs).
  • To assess the association between mesothelin expression and clinico-pathological parameters and survival outcomes in TETs.
  • To evaluate mesothelin as a potential therapeutic target for advanced thymic carcinomas.

Main Methods:

  • Immunohistochemistry was used to evaluate mesothelin expression in 71 tumor samples from patients with unresectable advanced TETs.
  • Samples included thymic carcinoma, thymoma, and thymic neuroendocrine tumors (NETs).
  • Expression levels were analyzed in relation to clinico-pathological data and patient survival, with blinded evaluation.

Main Results:

  • Mesothelin was expressed in 79% of thymic carcinomas, 10% of thymomas, and was absent in thymic NETs (P<0.0001).
  • In thymic carcinomas, 38% showed high mesothelin expression (in >50% of tumor cells) with strong, homogenous membranous staining.
  • Patients with high mesothelin expression in thymic carcinoma had significantly improved overall survival (median not reached) compared to those with low/no expression (1.60 years; HR=4.46, p=0.0026).

Conclusions:

  • Mesothelin is frequently expressed in advanced thymic carcinomas, infrequently in thymomas, and absent in thymic NETs.
  • The strong, membranous expression of mesothelin in thymic carcinoma positions it as a promising therapeutic target.
  • Targeting mesothelin may offer new treatment avenues for patients with advanced thymic carcinoma.
Keywords:
ImmunohistochemistryImmunotherapyMesothelinTherapeutic targetThymic carcinoma

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