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. 2011 Jan;137(1):73-80.
doi: 10.1007/s00432-010-0861-4. Epub 2010 Mar 18.

Reduced expression of EphB2 is significantly associated with nodal metastasis in Chinese patients with gastric cancer

Guanzhen Yu  1 , Yunshu Gao, Canrong Ni, Ying Chen, Jun Pan, Xi Wang, Zhiwei Ding, Jiejun Wang
Affiliations

Reduced expression of EphB2 is significantly associated with nodal metastasis in Chinese patients with gastric cancer

Guanzhen Yu et al. J Cancer Res Clin Oncol. 2011 Jan.

Abstract

Aims: EphB2 is a member of the Eph receptor tyrosine kinase family that has been involved in the regulation of cytoskeleton organization and cell migration in various cell types. Its role and regulation in carcinogenesis is controversial, especially in gastric cancer. We detected EphB2 expression and determined its clinical significance and explored its underlying molecular mechanism in gastric cancers.

Methods: Tissue microarray blocks containing primary gastric cancer, lymph node metastases, and adjacent normal mucosa specimens obtained from 337 Chinese patients were constructed. Expression of EphB2 in these specimens was analyzed using immunohistochemistry. Mutation analysis at the A9 tract in exon 17 and loss of heterozygosity analysis at the EphB2 gene locus were carried out in 13 sporadic EphB2-negative gastric cancers.

Results: Complete loss of EphB2 expression was observed in 177 (52.5%) of the 337 primary tumor and 41 (82%) of the 50 nodal metastases. Loss of EphB2 expression was significantly associated with advanced T stage, nodal metastasis, advanced disease stage, and poor histological differentiation. Loss of EphB2 expression correlated significantly with poor survival rates in both univariate and multivariate analysis. No frameshift mutation, but a higher frequency of allelic loss, was found in EphB2-negative primary and metastatic tumor samples.

Conclusions: Frequent deletion and decreased expression of EphB2 protein suggested it as a negative biomarker for gastric carcinogenesis and a potential predictor of the outcome of patients with gastric cancer.

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Figures

Fig. 1
Fig. 1
Analysis of EphB2 expression in human gastric cancers and adjacent normal mucosa specimens. a Normal (nonneoplastic) gastric mucosa; b gastric cancer-negative EphB2 expression (B1, intestinal; B2, diffuse); c positive expression of EphB2 in a well-differentiated (C1) and a moderately differentiated (C2) gastric caner, and lost EphB2 expression in a poorly differentiated gastric caner (C3). d Nodal metastases negative EphB2 expression; e Western blot analysis of three paired gastric cancer (T) and normal gastric mucosa specimens (N). Original magnification: 200×
Fig. 2
Fig. 2
Kaplan–Meier curves of survival durations in patients with gastric cancer treated with primary gastrectomy. a Patients with cancers negative for EphB2 expression had shorter survival durations than those with EphB2 expression in their gastric cancers (P < 0.01). b Subgroup analysis according to TNM stage showed patients with loss of EphB2 expression had poor survival to those with positive EphB2 expression in stage I–III (P < 0.01)
Fig. 3
Fig. 3
LOH analysis on chromosome 1p35–p36.1 in 13 EphB2-negative gastric cancers. a Schematic representation of LOH distribution. Case numbers are shown at the top. Microsatellite markers used are shown to the left box, primary tumor; circle, nodal metastases; filled box or circle, LOH; opened box or circle, retention of heterozygosity; shaded box or circle, not informative (homozygous). b Representative results of microsatellite analysis. DNAs of primary tumor (T), nodal metastasis (M), and corresponding normal (N) tissues are shown on the top with microsatellite markers at the bottom. Lost alleles in samples with LOH are depicted by arrows
See this image and copyright information in PMC

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