Oncotarget

Clinical Research Papers:

High mesothelin expression in advanced lung adenocarcinoma is associated with KRAS mutations and a poor prognosis

Anish Thomas, Yuanbin Chen, Seth M. Steinberg, Ji Luo, Svetlana Pack, Mark Raffeld, Zied Abdullaev, Christine Alewine, Arun Rajan, Giuseppe Giaccone, Ira Pastan, Markku Miettinen and Raffit Hassan _

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Oncotarget. 2015; 6:11694-11703. https://doi.org/10.18632/oncotarget.3429

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Abstract

Anish Thomas1, Yuanbin Chen1, Seth M. Steinberg2, Ji Luo3, Svetlana Pack4, Mark Raffeld4, Zied Abdullaev4, Christine Alewine5, Arun Rajan1, Giuseppe Giaccone6, Ira Pastan5, Markku Miettinen4, Raffit Hassan1

1Thoracic and GI Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

2Biostatistics and Data Management Section, Center for Cancer Research, National Institutes of Health, Bethesda, MD, USA

3Laboratory of Cancer Biology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

4Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

5Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

6Lombardi Cancer Center, Georgetown University, Washington DC, USA

Correspondence to:

Raffit Hassan, e-mail: [email protected]

Keywords: mesothelin, non-small cell lung cancer, KRAS, EGFR

Received: January 12, 2015     Accepted: February 24, 2015     Published: April 13, 2015

ABSTRACT

Mesothelin is a cell surface glycoprotein which is highly expressed in several epithelial cancers and may have a role in cell adhesion and metastases. In this study, we used prospectively obtained clinical and pathological data to characterize mesothelin expression in advanced lung adenocarcinoma. Tissue was obtained from patients who underwent molecular profiling of potentially actionable genes on a trial of molecular profiling and targeted therapies in advanced thoracic malignancies. We immunohistochemically evaluated the intensity, and the percentage of cells expressing mesothelin in 93 advanced lung adenocarcinomas. The evaluation was blinded for molecular data and outcome. Mutations of EGFR, KRAS, BRAF, AKT1, PIK3CA and HER2 were assessed by pyrosequencing; HER2 amplification and ALK translocation were assessed by fluorescence in situ hybridization. 53% of advanced lung adenocarcinomas expressed mesothelin to some degree; high mesothelin expression, defined as mesothelin positivity in more than 25% of cells, was found in 24% of patients. High mesothelin expression was associated with inferior survival (median 18.2 months vs. 32.9 months; P = 0.014). High mesothelin expression was strongly associated with mutant KRAS (P < 0.0001) and wild-type EGFR (P = 0.002). Our results provide strong rationale to explore anti-mesothelin targeted therapies in advanced lung adenocarcinoma especially in the KRAS-mutant subgroup.


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