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Mesothelin expression is associated with poor outcomes in breast cancer

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Abstract

Mesothelin is a potential therapeutic target and prognostic marker in breast cancer. However, results on its prognostic value in breast cancer have been equivocal and warranted further evaluation. We analyzed clinical data from two breast cancer patient cohorts comprising of 141 patients treated at our institution (discovery cohort) and 844 patients from The Cancer Genome Atlas (TCGA) (validation cohort). Mesothelin expression was quantified by immunohistochemistry or by RNA transcript levels as measured by whole-transcriptome sequencing in the discovery and validation cohorts respectively. Univariate analyses of data from the discovery cohort demonstrated that tumor size [hazard ratio (HR) = 1.30, 95 % confidence interval (CI) 1.11–1.51], positive (+) axillary lymph nodes (HR = 3.34; 95 % CI 1.51–7.39), and mesothelin expression (HR = 2.03; 95 % CI 1.10–3.74) were associated with disease-specific survival. Multivariate analyses demonstrated that mesothelin expression was significantly associated with worse survival (HR = 3.06, 95 % CI 1.40–6.68) after adjusting for (+) axillary lymph nodes and tumor size. Using TCGA cohort as validation dataset, mesothelin-expressing tumors were indeed significantly associated with worse overall survival with HR = 1.46; 95 % CI 1.05–2.03 and HR = 1.69; 95 % CI 1.17–2.42 in univariate and multivariate analyses respectively. Our results suggest that mesothelin is a prognostic breast tumor marker whose expression is highly enriched in triple negative breast cancer (TNBC) tumors. As there is no existing targeted therapy for TNBC, mesothelin may be a promising drug target for TNBC. Future work is needed to evaluate the efficacy of mesothelin directed targeted therapy in the treatment of breast cancer.

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Acknowledgments

This research was, in part, funded by the NCI Cancer Center Support Grant (2-P30-CA-016520-35) (J. Tchou), the Linda and Paul Richardson Breast Cancer Research Funds (J. Tchou), the Breast Cancer Immunotherapy Funds (J. Tchou), the 2013 Exceptional Project Award from the Breast Cancer Alliance (J. Tchou), the Pennsylvania Department of Health grant #0972501 (C.H. June), Fundacion Alonso Martin Escudero (A. Perales-Puchalt), and RO1 s CA178687 (J. Conejo-Garcia), CA157664 (J. Conejo-Garcia) and CA124515 (J. Conejo-Garcia). We thank the Bioinformatics Facility at The Wistar Institute for help with analyses of TCGA datasets. Y.R. Li is supported by the Paul and Daisy Soros Fellowship for New Americans and the NIH F30 Individual NRSA Training Grant.

Conflict of interest

All authors have declared no conflict of interest.

Author information

Author notes

  1. Rena R. Xian

    Present address: The Sidney Kimmel Comprehensive Cancer Center at John Hopkins, Baltimore, MD, USA

Authors and Affiliations

  1. Medical Scientist Training Program; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Yun R. Li

  2. The Center for Applied Genomics, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Yun R. Li

  3. Department of Pathology and Lab Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Rena R. Xian, Amy Ziober, Carl H. June & Paul J. Zhang

  4. Tumor Microenvironment and Metastasis Program, The Wistar Institute, Philadelphia, PA, USA

    Jose Conejo-Garcia & Alfredo Perales-Puchalt

  5. Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Carl H. June & Julia Tchou

  6. Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Carl H. June

  7. Division of Endocrine and Oncologic Surgery, Department of Surgery, and the Rena Rowan Breast Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Julia Tchou

  8. Perelman Center for Advanced Medicine, 3rd Floor West, 3400 Civic Center Boulevard, Philadelphia, PA, 19104-1693, USA

    Julia Tchou

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  1. Yun R. Li
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Correspondence to Julia Tchou.

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Li, Y.R., Xian, R.R., Ziober, A. et al. Mesothelin expression is associated with poor outcomes in breast cancer. Breast Cancer Res Treat 147, 675–684 (2014). https://doi.org/10.1007/s10549-014-3077-5

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  • DOI: https://doi.org/10.1007/s10549-014-3077-5

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