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Open Access Research article

EphA4 is a prognostic factor in gastric cancer

Kohji Miyazaki1, Mikito Inokuchi1*, Yoko Takagi2, Keiji Kato1, Kazuyuki Kojima3 and Kenichi Sugihara1

Author Affiliations

1 Department of Surgical Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan

2 Department of Translational Oncology, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

3 Department of Minimally Invasive Surgery, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan

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BMC Clinical Pathology 2013, 13:19  doi:10.1186/1472-6890-13-19

Published: 5 June 2013

Abstract

Background

Erythropoietin-producing hepatocellular (Eph) receptor, consisting of a family of receptor tyrosine kinases, plays critical roles in tumour development and is considered an attractive target for cancer therapy.

Methods

Tumour samples were obtained from 222 patients with gastric adenocarcinoma who underwent gastrectomy. The expressions of EphA2, EphA4, and ephrinA1 were evaluated immunohistochemically.

Results

High expressions of EphA2, EphA4, and ephrinA1 significantly correlated with variables related to tumour progression, including the depth of invasion, metastatic lymph nodes, pathological stage, and distant metastasis or recurrent disease. High expressions of EphA2, EphA4, and ephrinA1 were significantly associated with poorer disease-specific survival (DSS; p < 0.001, p < 0.001, p = 0.026). On multivariate analysis, EphA4 was an independent prognostic factor of DSS (hazard ratio [HR], 2.3; 95% confidence interval [CI], 1.1-4.8; p = 0.028), and EphA2 tended to be a prognostic factor (HR, 2.4; 95% CI, 1.0-5.8; p = 0.050). In stage II and III cancer, EphA4 and EphA2 were both significantly associated with shorter survival (p = 0.007 and 0.019), but only EphA2 was an independent prognostic factor (HR, 2.6; 95% CI, 1.1-6.3; p = 0.039).

Conclusion

EphA4 may play important roles in tumor progression and outcomes in patients with gastric cancer.

Keywords:
EphA4; EphA2; ephrinA1; Gastric cancer