Mesothelin is a specific biomarker of invasive cancer in the Barrett-associated adenocarcinoma progression model: translational implications for diagnosis and therapy

Alvarez, Hector; Rojas, Pamela Leal; Yong, Ken-Tye; Ding, Hong; Xu, Gaixia; Prasad, Paras N.; Wang, Jean; Canto, Marcia; Eshleman, James R.; Montgomery, Elizabeth A.; Maitra, Anirban

doi:10.1016/j.nano.2008.06.006

« Previous Next »Nanomedicine: Nanotechnology, Biology and Medicine
Volume 4, Issue 4 , Pages 295-301, December 2008

Mesothelin is a specific biomarker of invasive cancer in the Barrett-associated adenocarcinoma progression model: translational implications for diagnosis and therapy

Hector Alvarez, MD
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Pamela Leal Rojas, MD
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Ken-Tye Yong, PhD
- Institute for Lasers, Photonics, and Biophotonics, Department of Chemistry, State University of New York, Buffalo, New York, USA
Hong Ding, PhD
- Institute for Lasers, Photonics, and Biophotonics, Department of Chemistry, State University of New York, Buffalo, New York, USA
Gaixia Xu, PhD
- Institute for Lasers, Photonics, and Biophotonics, Department of Chemistry, State University of New York, Buffalo, New York, USA
Paras N. Prasad, PhD
- Institute for Lasers, Photonics, and Biophotonics, Department of Chemistry, State University of New York, Buffalo, New York, USA
Jean Wang, MD
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Marcia Canto, MD
- Division of Gastroenterology and Hepatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
James R. Eshleman, MD, PhD
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Elizabeth A. Montgomery, MD
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
Anirban Maitra, MBBS
- Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
- Corresponding author. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.

Received 13 January 2008; accepted 25 June 2008. published online 11 August 2008.

Abstract

Esophageal adenocarcinoma arises in the backdrop of Barrett metaplasia-dysplasia sequence, with the vast majority of patients presenting with late-stage malignancy. Mesothelin, a glycophosphatidylinositol-anchored protein, is aberrantly overexpressed on the surface of many solid cancers. Mesothelin expression was assessed in esophageal tissue microarrays encompassing the entire histological spectrum of Barrett-associated dysplasia and adenocarcinoma. Mesothelin expression was observed in 24/84 (29%) of invasive adenocarcinomas and in 5/34 (15%) lymph node metastases. In contrast, normal squamous and cardiac mucosa, as well as noninvasive Barrett lesions, failed to label with mesothelin. Mesothelin was expressed in the esophageal adenocarcinoma cell line JH-EsoAd1 but not in primary human esophageal epithelial cells. Anti-mesothelin antibody–conjugated CdSe/CDS/ZnS quantum rods were synthesized, and confocal bioimaging confirmed robust binding to JH-EsoAd1 cells. Anti-mesothelin antibody–conjugated nanoparticles can be useful for the diagnosis and therapy of mesothelin-overexpressing esophageal adenocarcinomas.

Key words: Barrett esophagus, Mesothelin, Immunohistochemistry, Quantum rods, Antibody-conjugated nanoparticles, Molecular imaging