Evaluation of EphA2 and EphB4 as Targets for Image-Guided Colorectal Cancer Surgery.
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.
Department of Radiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. m.a.stammes@lumc.nl.|Percuros B.V., 2333 CL Leiden, The Netherlands. m.a.stammes@lumc.nl.
Marieke A
MA
Stammes
Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. h.a.j.m.prevoo@lumc.nl.
Hendrica A J M
HA
Prevoo
Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. m.c.terhorst@lumc.nl.
Meyke C
MC
Ter Horst
Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. s.a.groot@lumc.nl.
Stéphanie A
SA
Groot
Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. c.j.h.vandevelde@lumc.nl.
Cornelis J H
CJ
Van de Velde
Percuros B.V., 2333 CL Leiden, The Netherlands. achan@percuros.com.
Alan B
AB
Chan
Department of Radiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Lioe-Fee
LF
de Geus-Oei
Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. p.j.k.kuppen@lumc.nl.
Peter J K
PJ
Kuppen
Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. a.l.vahrmeijer@lumc.nl.
Alexander L
AL
Vahrmeijer
Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. elenap@sbpdiscovery.org.
Elena B
EB
Pasquale
Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. c.f.m.sier@lumc.nl.|Antibodies for Research Applications B.V., 2805 HT Gouda, The Netherlands. c.f.m.sier@lumc.nl.
Cornelis F M
CF
Sier
D000328:Adult; D000368:Aged; D015415:Biomarkers; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000378:metabolism* / Q000601:surgery*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D036104:Receptor, EphA2 / Q000378:metabolism*; D036122:Receptor, EphA4 / Q000378:metabolism*; D025321:Surgery, Computer-Assisted / Q000379:methods
D015415:Biomarkers; D036104:Receptor, EphA2; D036122:Receptor, EphA4
cancer imaging; colon cancer; immunohistochemistry; normal tissue; tissue microarray; tyrosine kinase receptor