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Updated: Mar 7, 2026

Colorectal Cancer Cell Surface Protein Profiling Using an Antibody Microarray and Fluorescence Multiplexing
Published on: September 25, 2011
Evaluation of EphA2 and EphB4 as Targets for Image-Guided Colorectal Cancer Surgery
Marieke A Stammes1,2, Hendrica A J M Prevoo3, Meyke C Ter Horst4
1Department of Radiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. m.a.stammes@lumc.nl.
Abstract:
Targeted image-guided oncologic surgery (IGOS) relies on the recognition of cell surface-associated proteins, which should be abundantly present on tumor cells but preferably absent on cells in surrounding healthy tissue. The transmembrane receptor tyrosine kinase EphA2, a member of the A class of the Eph receptor family, has been reported to be highly overexpressed in several tumor types including breast, lung, brain, prostate, and colon cancer and is considered amongst the most promising cell membrane-associated tumor antigens by the NIH. Another member of the Eph receptor family belonging to the B class, EphB4, has also been found to be upregulated in multiple cancer types. In this study, EphA2 and EphB4 are evaluated as targets for IGOS of colorectal cancer by immunohistochemistry (IHC) using a tissue microarray (TMA) consisting of 168 pairs of tumor and normal tissue. The IHC sections were scored for staining intensity and percentage of cells stained. The results show a significantly enhanced staining intensity and more widespread distribution in tumor tissue compared with adjacent normal tissue for EphA2 as well as EphB4. Based on its more consistently higher score in colorectal tumor tissue compared to normal tissue, EphB4 appears to be a promising candidate for IGOS of colorectal cancer. In vitro experiments using antibodies on human colon cancer cells confirmed the possibility of EphB4 as target for imaging.
Insights
EphA2 and EphB4 are promising cell surface targets for image-guided oncologic surgery (IGOS) in colorectal cancer. EphB4 shows higher tumor specificity, making it a strong candidate for enhanced cancer imaging and treatment.
Area of Science:
- Oncology
- Molecular Biology
- Surgical Innovation
Background:
- Targeted image-guided oncologic surgery (IGOS) requires specific cell surface markers abundant in tumors but absent in healthy tissues.
- EphA2 and EphB4, members of the Eph receptor tyrosine kinase family, are implicated in various cancers.
- EphA2 is a highly overexpressed tumor antigen in multiple cancer types, including colon cancer.
Purpose of the Study:
- To evaluate EphA2 and EphB4 as potential targets for IGOS in colorectal cancer.
- To assess the expression patterns of EphA2 and EphB4 in colorectal tumors versus normal adjacent tissues.
Main Methods:
- Immunohistochemistry (IHC) was performed on a tissue microarray (TMA) of 168 colorectal tumor and normal tissue pairs.
- Staining intensity and percentage of positive cells for EphA2 and EphB4 were scored.
- In vitro experiments utilized antibodies on human colon cancer cells to confirm target potential.
Main Results:
- Both EphA2 and EphB4 demonstrated significantly higher staining intensity and wider distribution in tumor tissues compared to normal tissues.
- EphB4 exhibited more consistent and higher expression scores in colorectal tumors relative to normal tissue.
- In vitro studies confirmed EphB4's viability as a target for imaging applications.
Conclusions:
- EphA2 and EphB4 are valid targets for IGOS in colorectal cancer.
- EphB4 presents as a particularly promising candidate due to its enhanced tumor specificity.
- Further development of EphB4-targeting agents could improve colorectal cancer imaging and surgical guidance.
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