Skip to main content
Top
Published in: Annals of Surgical Oncology 5/2011

01-05-2011 | Translational Research and Biomarkers

Influence of A9 Region Mutation in EphB2 Gene in the Prognosis of Patients with Colorectal Adenocarcinoma

Authors: M. Vidaurreta, PhD, S. Rafael, PhD, S. Veganzones, PhD, V. de la Orden, PhD, C. Fernández, MD, R. Gómez-Casaseca, BD, J. Cerdán, MD, M. Maestro, PhD

Published in: Annals of Surgical Oncology | Issue 5/2011

Login to get access

Abstract

Background

EphB2 is a transmembrane glycoprotein implicated in the regulation of cell growth, differentiation, and motility. It has been proposed as a tumor suppressor gene, and the role of EphB2 protein in tumorogenesis has been demonstrated. The aim of this study was to test the influence of mutation of A9 region in EphB2 gene in the prognosis of patients with sporadic CCR.

Materials and Methods

A total of 473 patients with colorectal cancer were included. A9 region in exon 17 of EphB2 was amplified using specific primer and analyzed using Genescan. All mutations were confirmed by direct sequencing.

Results

EphB2 mutation was detected in 13 of the 473 patients (2.7%). Mutation of EphB2 showed association with tumor site, 12 of 13 mutations were proximal tumors (P < 0.001). EphB2 mutation confers better prognosis in the adenocarcinoma group; 100% of patients carrying the mutation survived and were disease free after 72 months (P = 0.02 and 0.03, respectively).

Conclusions

Despite the low frequency of EphB2 gene, we got promising results. It would be very interesting to increase the population size to verify our results. If these findings are confirmed, EphB2 could help discriminate patients with adenocarcinoma with different prognosis and to improve the election of the most suitable treatment in each case.
Literature
2.
go back to reference Ferlay J, Bray F, Pisan P, Parkin DM. Globocan 2000: cancer incidence, mortality and prevalence worldwide. France: IARC Press; 2001. Ferlay J, Bray F, Pisan P, Parkin DM. Globocan 2000: cancer incidence, mortality and prevalence worldwide. France: IARC Press; 2001.
3.
go back to reference Skibber JM, Minsky BD, Hoff PM. Cancer of the colon. Chapter 33.7. In: De Vita VT, Hellman S, Rosenberg SA, editors. Cancer Principles and Practice of Oncology. 6th ed. Lippincott Williams and Wilkins, Philadelphia, PA, 2001. Skibber JM, Minsky BD, Hoff PM. Cancer of the colon. Chapter 33.7. In: De Vita VT, Hellman S, Rosenberg SA, editors. Cancer Principles and Practice of Oncology. 6th ed. Lippincott Williams and Wilkins, Philadelphia, PA, 2001.
4.
go back to reference Cancer Trends Progress Report—2009/2010 Update, National Cancer Institute, NIH, DHHS, Bethesda, MD, April 2010. Cancer Trends Progress Report—2009/2010 Update, National Cancer Institute, NIH, DHHS, Bethesda, MD, April 2010.
5.
go back to reference Vogelstein B, Fearon E, Hamilton S, Kern S, Preisinger A, Leppert M, et al. Genetic alterations during colorectal tumor development. N Engl J Med. 1988;319:525–32.PubMedCrossRef Vogelstein B, Fearon E, Hamilton S, Kern S, Preisinger A, Leppert M, et al. Genetic alterations during colorectal tumor development. N Engl J Med. 1988;319:525–32.PubMedCrossRef
6.
go back to reference Batlle E, Henderson JT, Beghtel H, van den Born MM, Sancho E, Huls G, et al. Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell. 2002;111:251–63.PubMedCrossRef Batlle E, Henderson JT, Beghtel H, van den Born MM, Sancho E, Huls G, et al. Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB/ephrinB. Cell. 2002;111:251–63.PubMedCrossRef
7.
go back to reference Eph Nomenclature Committee, Unified nomenclature for Eph family receptors and their ligands, the ephrins. Cell. 1997;90:403–4. Eph Nomenclature Committee, Unified nomenclature for Eph family receptors and their ligands, the ephrins. Cell. 1997;90:403–4.
9.
go back to reference Batlle E, Bacani J, Gegthel H, Jonkheer S, Gregorieff A, van de Born M, et al. EphB receptor activity suppresses colorectal cancer progression. Nature. 2005;435:1126–30.PubMedCrossRef Batlle E, Bacani J, Gegthel H, Jonkheer S, Gregorieff A, van de Born M, et al. EphB receptor activity suppresses colorectal cancer progression. Nature. 2005;435:1126–30.PubMedCrossRef
10.
go back to reference Ikegaki N, Tang XX, Liu XG, Biegel JA, Allen C, Yoshioka EP, et al. Molecular characterization and chromosomal localization of DRT (EPHT3): adevelopmentally regulated human protein-tyrosine kinase gene of the EPH family. Hum. Mol Gen. 1995;4:2033–45.PubMedCrossRef Ikegaki N, Tang XX, Liu XG, Biegel JA, Allen C, Yoshioka EP, et al. Molecular characterization and chromosomal localization of DRT (EPHT3): adevelopmentally regulated human protein-tyrosine kinase gene of the EPH family. Hum. Mol Gen. 1995;4:2033–45.PubMedCrossRef
11.
go back to reference Alazzouzi H, Davalos V, Kokko A, Domingo E, Woerner SM, Wilson AJ, et al. Mechanisms of inactivation of the receptor tyrosine kinase EPHB2 in colorectal tumors. Cancer Res. 2005;65:10170–73.PubMedCrossRef Alazzouzi H, Davalos V, Kokko A, Domingo E, Woerner SM, Wilson AJ, et al. Mechanisms of inactivation of the receptor tyrosine kinase EPHB2 in colorectal tumors. Cancer Res. 2005;65:10170–73.PubMedCrossRef
12.
go back to reference Cerdán J. Seguimiento de los pacientes intervenidos de cáncer colorrectal. Rev Cancer. 1997;11:32–41. Cerdán J. Seguimiento de los pacientes intervenidos de cáncer colorrectal. Rev Cancer. 1997;11:32–41.
13.
go back to reference Davalos V, Dopeso H, Velho S, Ferreira AM, Cirnes L, Diaz-Chico N, et al. High EphB2 mutation rate in gastric but not endometrial tumors with microsatellite instability. Oncogene. 2007;26:308–11.PubMedCrossRef Davalos V, Dopeso H, Velho S, Ferreira AM, Cirnes L, Diaz-Chico N, et al. High EphB2 mutation rate in gastric but not endometrial tumors with microsatellite instability. Oncogene. 2007;26:308–11.PubMedCrossRef
14.
go back to reference Guo DL, Zhang J, Yues ST, Tsui WY, Chan AS, Ho C, et al. Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumors. Carcinogenesis. 2006;27:454–64.PubMedCrossRef Guo DL, Zhang J, Yues ST, Tsui WY, Chan AS, Ho C, et al. Reduced expression of EphB2 that parallels invasion and metastasis in colorectal tumors. Carcinogenesis. 2006;27:454–64.PubMedCrossRef
15.
go back to reference Lugli A, Spichtin H, Maurer R, Mirlacher M, Kiefer J, Huusko P, et al. EphB2 expression across 138 human tumor types in a tissue microarray: high levels of expression in gastrointestinal cancer. Clin Cancer Res. 2005;11:6450–8.PubMedCrossRef Lugli A, Spichtin H, Maurer R, Mirlacher M, Kiefer J, Huusko P, et al. EphB2 expression across 138 human tumor types in a tissue microarray: high levels of expression in gastrointestinal cancer. Clin Cancer Res. 2005;11:6450–8.PubMedCrossRef
16.
go back to reference Song JH, Kim CJ, Cho YG, Kwak HH, Nam SW, Yoo NJ, et al. Genetic and epigenetic analysis of the EPHB2 gene in gastric cancers. APMIS. 2007;115:164–8.PubMedCrossRef Song JH, Kim CJ, Cho YG, Kwak HH, Nam SW, Yoo NJ, et al. Genetic and epigenetic analysis of the EPHB2 gene in gastric cancers. APMIS. 2007;115:164–8.PubMedCrossRef
17.
go back to reference Maestro ML, Vidaurreta M, Sanz-Casla MT, Rafael S, Veganzones S, Martínez A, et al. Role of the BRAF mutations in the microsatellite instability genetic pathway in sporadic colorectal cancer. Ann Surg Oncol. 2007;14:1229–36.PubMedCrossRef Maestro ML, Vidaurreta M, Sanz-Casla MT, Rafael S, Veganzones S, Martínez A, et al. Role of the BRAF mutations in the microsatellite instability genetic pathway in sporadic colorectal cancer. Ann Surg Oncol. 2007;14:1229–36.PubMedCrossRef
Metadata
Title
Influence of A9 Region Mutation in EphB2 Gene in the Prognosis of Patients with Colorectal Adenocarcinoma
Authors
M. Vidaurreta, PhD
S. Rafael, PhD
S. Veganzones, PhD
V. de la Orden, PhD
C. Fernández, MD
R. Gómez-Casaseca, BD
J. Cerdán, MD
M. Maestro, PhD
Publication date
01-05-2011
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 5/2011
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-010-1448-7

Other articles of this Issue 5/2011

Annals of Surgical Oncology 5/2011 Go to the issue