Oncotarget

Research Papers:

Comprehensive immunohistochemical study of mesothelin (MSLN) using different monoclonal antibodies 5B2 and MN-1 in 1562 tumors with evaluation of its prognostic value in malignant pleural mesothelioma

Shingo Inaguma _, Zengfeng Wang, Jerzy Lasota, Masanori Onda, Piotr Czapiewski, Renata Langfort, Janusz Rys, Joanna Szpor, Piotr Waloszczyk, Krzysztof Okoń, Wojciech Biernat, Hiroshi Ikeda, David S. Schrump, Raffit Hassan, Ira Pastan and Markku Miettinen

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Oncotarget. 2017; 8:26744-26754. https://doi.org/10.18632/oncotarget.15814

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Abstract

Shingo Inaguma1,2, Zengfeng Wang1, Jerzy Lasota1, Masanori Onda3, Piotr Czapiewski4,5, Renata Langfort6, Janusz Rys7, Joanna Szpor8, Piotr Waloszczyk9, Krzysztof Okoń8, Wojciech Biernat4, Hiroshi Ikeda2, David S. Schrump10, Raffit Hassan10, Ira Pastan3, Markku Miettinen1

1Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA

2Department of Pathology, Aichi Medical University School of Medicine, Nagakute, Japan

3 Laboratory of Molecular Biology, National Cancer Institute, Bethesda, MD, USA

4Department of Pathomorphology, Medical University of Gdansk, Gdansk, Poland

5Department of Pathology, Otto-von-Guericke University Magdeburg, Magdeburg, Germany

6Department of Pathology, National Tuberculosis and Lung Diseases Research Institute, Warsaw, Poland

7Department of Tumor Pathology, Centre of Oncology, Maria Sklodowska-Curie Memorial Institute, Krakow Branch, Poland

8Department of Pathomorphology, Jagiellonian University, Krakow, Poland

9Independent Laboratory of Pathology, Zdunomed, Szczecin, Poland

10Thoracic and GI Oncology Branch, National Cancer Institute, Bethesda, MD, USA

Correspondence to:

Shingo Inaguma, email: inaguma@aichi-med-u.ac.jp

Keywords: mesothelin (MSLN), immunohistochemistry, 5B2, MN-1, malignant pleural mesothelioma

Received: October 05, 2016     Accepted: February 15, 2017     Published: March 01, 2017

ABSTRACT

Mesothelin (MSLN) is a glycophosphatidylinositol (GPI)-linked cell surface protein highly expressed in several types of malignant tumors sometimes in association with increased tumor aggressiveness and poor clinical outcome. In the present study, 1562 tumors were immunohistochemically analyzed for mesothelin expression using two different types of mouse monoclonal antibodies (5B2 and MN-1) to determine the clinical usefulness of mesothelin immunohistochemistry as well as to pinpoint potential targets for future anti-mesothelin therapy. Also, characterization of selected mesothelin-positive tumors was performed by immunohistochemistry and oncogene sequencing. Among the tumors analyzed, the highest frequencies of mesothelin-positivity were detected in ovarian serous carcinoma (90% in 5B2 and 94% in MN-1). Both antibodies showed frequent positivity in pancreatic adenocarcinoma (71% using 5B2 and 87% using MN-1) and malignant pleural mesothelioma (75% using 5B2 and 78% using MN-1). In malignant mesothelioma, overall survival was significantly longer in the cohort of patients with diffuse membranous expression of mesothelin (P < 0.001). Both antibodies showed positive staining in thymic carcinoma (77% in 5B2 and 59% in MN-1), however, no expression was detected in thymoma. No correlation was detected between mesothelin expression and mismatch repair system deficient phenotype or gene mutation (BRAF and RAS) status in gastrointestinal adenocarcinomas. Mesothelin immunohistochemistry may assist the differential diagnosis of thymoma vs. thymic carcinoma as well as prognostication of mesothelioma patients. Our results demonstrate that patients with solid tumors expressing mesothelin could be targeted by anti-mesothelin therapies.


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