title: The use of sensitive chemical antibodies for diagnosis: detection of low levels of EpCAM in breast cancer.
abstract: EpCAM is expressed at low levels in a variety of normal human epithelial tissues, but is overexpressed in 70-90% of carcinomas. From a clinico-pathological point of view, this has both prognostic and therapeutic significance. EpCAM was first suggested as a therapeutic target for the treatment of epithelial cancers in the 1990s. However, following several immunotherapy trials, the results have been mixed. It has been suggested that this is due, at least in part, to an unknown level of EpCAM expression in the tumors being targeted. Thus, selection of patients who would benefit from EpCAM immunotherapy by determining EpCAM status in the tumor biopsies is currently undergoing vigorous evaluation. However, current EpCAM antibodies are not robust enough to be able to detect EpCAM expression in all pathological tissues. Here we report a newly developed EpCAM RNA aptamer, also known as a chemical antibody, which is not only specific but also more sensitive than current antibodies for the detection of EpCAM in formalin-fixed paraffin-embedded primary breast cancers. This new aptamer, together with our previously described aptamer, showed no non-specific staining or cross-reactivity with tissues that do not express EpCAM. They were able to reliably detect target proteins in breast cancer xenograft where an anti-EpCAM antibody (323/A3) showed limited or no reactivity. Our results demonstrated a more robust detection of EpCAM using RNA aptamers over antibodies in clinical samples with chromogenic staining. This shows the potential of aptamers in the future of histopathological diagnosis and as a tool to guide targeted immunotherapy.
authors: School of Medicine, Deakin University, Waurn Ponds, Victoria, Australia.
authors: Sarah
authors: S
authors: Shigdar
authors: Christine
authors: C
authors: Qian
authors: Li
authors: L
authors: Lv
authors: Chunwen
authors: C
authors: Pu
authors: Yong
authors: Y
authors: Li
authors: Lianhong
authors: L
authors: Li
authors: Manju
authors: M
authors: Marappan
authors: Jia
authors: J
authors: Lin
authors: Lifen
authors: L
authors: Wang
authors: Wei
authors: W
authors: Duan
mesh_terms: D000818:Animals; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000378:metabolism*; D052157:Aptamers, Nucleotide / Q000378:metabolism; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000276:immunology* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D000071858:Epithelial Cell Adhesion Molecule; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008207:Lymphatic Metastasis / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D016612:Paraffin Embedding; D012680:Sensitivity and Specificity; D013194:Staining and Labeling; D023041:Xenograft Model Antitumor Assays
chemical_list: D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; D052157:Aptamers, Nucleotide; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule