Evaluation of EphA2 and EphB4 as Targets for Image-Guided Colorectal Cancer Surgery.

Marieke Stammes,Hendrica Prevoo,Peter Kuppen,Alan Chan,Lioe-Fee De Geus-Oei,Elena Pasquale,Cornelis Van De Velde,Cornelis Sier,Meyke Ter Horst,Stéphanie Groot,Alexander Vahrmeijer

doi:10.3390/ijms18020307

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.

Highlights

During oncologic surgery, there is limited information available about the exact boundaries between tumor and healthy tissue
We decided to evaluate one of the candidates on the list, EphA2, a member of the Eph family of receptor tyrosine kinases that is preferentially expressed in tumor tissue compared to normal tissue and plays an important role in cancer malignancy [4,5]
In this study, we evaluated whether the EphA2 receptor and the related EphB4 receptor are suitable for use in image-guided colorectal cancer surgery [5,6,7,12,13]

Summary

Introduction

There is limited information available about the exact boundaries between tumor and healthy tissue. Receptors and adhesion molecules upregulated on the surface of tumor cells are the best candidates for targeted cancer imaging, but the ideal protein for colorectal cancer imaging has not yet been identified [3]. We decided to evaluate one of the candidates on the list, EphA2, a member of the Eph family of receptor tyrosine kinases that is preferentially expressed in tumor tissue compared to normal tissue and plays an important role in cancer malignancy [4,5]. As a target for tumor imaging, a low grade of expression of both EphA2 and EphB4 in normal tissue is essential and has not been thoroughly investigated [5,6,7]

Methods

Results

Conclusion