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

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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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Abbreviations

LN:

Lymph node

TMA:

Tissue microarray

LOH:

Loss of heterozygosity

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Conflict of interest statement

We declare no conflicts of interest with any other person or units.

Author information

Correspondence to Jiejun Wang.

Additional information

G. Yu and Y. Gao contributed equally to this work.

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Yu, G., Gao, Y., Ni, C. et al. Reduced expression of EphB2 is significantly associated with nodal metastasis in Chinese patients with gastric cancer. J Cancer Res Clin Oncol 137, 73–80 (2011). https://doi.org/10.1007/s00432-010-0861-4

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Keywords

  • Gastric carcinoma
  • Immunohistochemistry
  • Mutation
  • LOH
  • EphB2