This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lugli, A. Articles by Tornillo, L. Search for Related Content PubMed PubMed Citation Articles by Lugli, A. Articles by Tornillo, L.

EphB2 Expression across 138 Human Tumor Types in a Tissue Microarray: High Levels of Expression in Gastrointestinal Cancers

Authors' Affiliations: ¹ Institute of Pathology, University Hospital and ² Institute of Clinical Pathology, Basel, Switzerland; ³ Institute of Pathology, Stadtspital Triemli, Zurich, Switzerland; ⁴ Translational Genomics Research Institute, Cancer Drug Development Laboratory, Gaithersburg, Maryland; and ⁵ Medical Biotechnology, VTT Technical Research Centre of Finland and the University of Turku, Turku, Finland

Requests for reprints: Luigi Tornillo, Institute of Pathology, University Hospital, Schönbeinstrasse 40, 4031 Basel, Switzerland. Phone: 41-61-265-26-49; Fax: 41-61-265-31-94; E-mail: tornillol{at}uhbs.ch.

Purpose: To comprehensively evaluate ephrin receptor B2 (EphB2) expression in normal and neoplastic tissues. EphB2 is a tyrosine kinase recently implicated in the deregulation of cell-to-cell communication in many tumors.

Experimental Design: EphB2 protein expression was analyzed by immunohistochemistry on tissue microarrays that included 76 different normal tissues, >4,000 samples from 138 different cancer types, and 1,476 samples of colon cancer with clinical follow-up data.

Results: We found most prominent EphB2 expression in the intestinal epithelium (colonic crypts) with cancer of the colorectum displaying the highest EphB2 positivity of all tumors. Positivity was found in 100% of 118 colon adenomas but in 33.3% of 45 colon carcinomas. EphB2 expression was also observed in 75 tumor categories, including serous carcinoma of the endometrium (34.8%), adenocarcinoma of the esophagus (33.3%), intestinal adenocarcinoma of the stomach (30.2%), and adenocarcinoma of the small intestine (70%). The occasional finding of strong EphB2 positivity in tumors without EphB2 positivity in the corresponding normal cells [adenocarcinoma of the lung (4%) and pancreas (2.2%)] suggests that deregulation of EphB2 signaling may involve up-regulation of the protein expression. In colon carcinoma, loss of EphB2 expression was associated with advanced stage (P < 0.0001) and was an indicator of poor overall survival (P = 0.0098).

Conclusions: Our results provide an overview on the EphB2 protein expression in normal and neoplastic tissues. Deregulated EphB2 expression may play a role in several cancer types with loss of EphB2 expression serving as an indicator of the possible pathogenetic role of EphB2 signaling in the maintenance of tissue architecture of colon epithelium.

This article has been cited by other articles:

				I. Zlobec, K. Baker, L. M. Terracciano, and A. Lugli RHAMM, p21 Combined Phenotype Identifies Microsatellite Instability-High Colorectal Cancers with a Highly Adverse Prognosis Clin. Cancer Res., June 15, 2008; 14(12): 3798 - 3806. [Abstract] [Full Text] [PDF]

				M. Lackmann and A. W. Boyd Eph, a Protein Family Coming of Age: More Confusion, Insight, or Complexity? Sci. Signal., April 15, 2008; 1(15): re2 - re2. [Abstract] [Full Text] [PDF]

				H. Li, X. Fan, R. C. Kovi, Y. Jo, B. Moquin, R. Konz, C. Stoicov, E. Kurt-Jones, S. R. Grossman, S. Lyle, et al. Spontaneous Expression of Embryonic Factors and p53 Point Mutations in Aged Mesenchymal Stem Cells: A Model of Age-Related Tumorigenesis In Mice Cancer Res., November 15, 2007; 67(22): 10889 - 10898. [Abstract] [Full Text] [PDF]

				H. Nakanishi, T. Nakamura, E. Canaani, and C. M. Croce ALL1 fusion proteins induce deregulation of EphA7 and ERK phosphorylation in human acute leukemias PNAS, September 4, 2007; 104(36): 14442 - 14447. [Abstract] [Full Text] [PDF]

				F. Bertucci, D. Birnbaum, and A. Goncalves Proteomics of Breast Cancer: Principles and Potential Clinical Applications Mol. Cell. Proteomics, October 1, 2006; 5(10): 1772 - 1786. [Abstract] [Full Text] [PDF]

				M. Nakada, K. L. Drake, S. Nakada, J. A. Niska, and M. E. Berens Ephrin-B3 Ligand Promotes Glioma Invasion through Activation of Rac1. Cancer Res., September 1, 2006; 66(17): 8492 - 8500. [Abstract] [Full Text] [PDF]

				H. Clevers and E. Batlle EphB/EphrinB Receptors and Wnt Signaling in Colorectal Cancer Cancer Res., January 1, 2006; 66(1): 2 - 5. [Abstract] [Full Text] [PDF]