Mesothelin is a specific biomarker of invasive cancer in the Barrett-associated adenocarcinoma progression model: translational implications for diagnosis and therapy.
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.
Alvarez
Hector
H
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Rojas
Pamela Leal
PL
Yong
Ken-Tye
KT
Ding
Hong
H
Xu
Gaixia
G
Prasad
Paras N
PN
Wang
Jean
J
Canto
Marcia
M
Eshleman
James R
JR
Montgomery
Elizabeth A
EA
Maitra
Anirban
A
D000230:Adenocarcinoma / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D000906:Antibodies / Q000276:immunology / Q000627:therapeutic use; D001471:Barrett Esophagus / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000276:immunology; D015153:Blotting, Western; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism*; D058851:GPI-Linked Proteins; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000276:immunology; D000090204:Mesothelin; D018613:Microscopy, Confocal; D053758:Nanoparticles; D046888:Tissue Array Analysis
D000906:Antibodies; D014408:Biomarkers, Tumor; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; D000090204:Mesothelin