PMID- 28165374 OWN - NLM STAT- MEDLINE DCOM- 20170420 LR - 20220129 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 18 IP - 2 DP - 2017 Feb 3 TI - Evaluation of EphA2 and EphB4 as Targets for Image-Guided Colorectal Cancer Surgery. LID - 10.3390/ijms18020307 [doi] LID - 307 AB - 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. FAU - Stammes, Marieke A AU - Stammes MA AD - Department of Radiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. m.a.stammes@lumc.nl. AD - Percuros B.V., 2333 CL Leiden, The Netherlands. m.a.stammes@lumc.nl. FAU - Prevoo, Hendrica A J M AU - Prevoo HA AD - Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. h.a.j.m.prevoo@lumc.nl. FAU - Ter Horst, Meyke C AU - Ter Horst MC AD - Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. m.c.terhorst@lumc.nl. FAU - Groot, Stephanie A AU - Groot SA AD - Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. s.a.groot@lumc.nl. FAU - Van de Velde, Cornelis J H AU - Van de Velde CJ AD - Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. c.j.h.vandevelde@lumc.nl. FAU - Chan, Alan B AU - Chan AB AD - Percuros B.V., 2333 CL Leiden, The Netherlands. achan@percuros.com. FAU - de Geus-Oei, Lioe-Fee AU - de Geus-Oei LF AD - Department of Radiology, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. FAU - Kuppen, Peter J K AU - Kuppen PJ AD - Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. p.j.k.kuppen@lumc.nl. FAU - Vahrmeijer, Alexander L AU - Vahrmeijer AL AD - Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. a.l.vahrmeijer@lumc.nl. FAU - Pasquale, Elena B AU - Pasquale EB AD - Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92037, USA. elenap@sbpdiscovery.org. FAU - Sier, Cornelis F M AU - Sier CF AD - Department of Surgery, Leiden University Medical Center, 2300 RC Leiden, The Netherlands. c.f.m.sier@lumc.nl. AD - Antibodies for Research Applications B.V., 2805 HT Gouda, The Netherlands. c.f.m.sier@lumc.nl. LA - eng GR - 323105/ERC_/European Research Council/International GR - P01 CA138390/CA/NCI NIH HHS/United States PT - Journal Article DEP - 20170203 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Biomarkers) RN - EC 2.7.10.1 (Receptor, EphA2) RN - EC 2.7.10.1 (Receptor, EphA4) SB - IM MH - Adult MH - Aged MH - Biomarkers MH - Cell Line, Tumor MH - Colorectal Neoplasms/diagnosis/*metabolism/*surgery MH - Female MH - Humans MH - Immunohistochemistry MH - Male MH - Middle Aged MH - Neoplasm Grading MH - Neoplasm Staging MH - Receptor, EphA2/*metabolism MH - Receptor, EphA4/*metabolism MH - *Surgery, Computer-Assisted/methods PMC - PMC5343843 OTO - NOTNLM OT - cancer imaging OT - colon cancer OT - immunohistochemistry OT - normal tissue OT - tissue microarray OT - tyrosine kinase receptor COIS- The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. EDAT- 2017/02/07 06:00 MHDA- 2017/04/21 06:00 PMCR- 2017/02/01 CRDT- 2017/02/07 06:00 PHST- 2016/11/23 00:00 [received] PHST- 2016/12/30 00:00 [revised] PHST- 2017/01/21 00:00 [accepted] PHST- 2017/02/07 06:00 [entrez] PHST- 2017/02/07 06:00 [pubmed] PHST- 2017/04/21 06:00 [medline] PHST- 2017/02/01 00:00 [pmc-release] AID - ijms18020307 [pii] AID - ijms-18-00307 [pii] AID - 10.3390/ijms18020307 [doi] PST - epublish SO - Int J Mol Sci. 2017 Feb 3;18(2):307. doi: 10.3390/ijms18020307.