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Human epidermal growth factor receptor-2 expression in primary and metastatic gastric cancer

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Abstract

Background

Amplification and overexpression of human epidermal growth factor receptor-2 (HER-2) has been shown in subgroups of gastric cancer, correlated to more aggressive disease and predictive for the treatment with HER-2 antibodies. In this study, we examined the prognostic value of HER-2 expression in primary gastric cancer and in associated lymph node metastases and confirmed the role of HER-2 in tumor angiogenesis by examining vascular endothelial growth factor (VEGF) expression.

Methods

Immunohistochemistry was used to detect HER-2 and VEGF expression in 110 gastric cancer specimens and associated lymph node metastases and in 96 specimens of normal gastric mucosa.

Results

The expression level of HER-2 in gastric tissues was significantly higher than in normal tissues (19.1 % vs. 8.3 %; P < 0.05). HER-2 overexpression was homogeneous in primary gastric cancer and metastatic lymph nodes (P = 0.607). There was a significant positive correlation of HER-2 expression and VEGF expression (P = 0.007). HER-2 overexpression in primary tumor correlated with lymph node metastasis, distant metastasis, and American Joint Committee on Cancer (AJCC) stage. Cox regression multivariate analyses confirmed that tumor size, histological grade, lymph node ratio, AJCC stage, chemotherapy, and HER-2 expression were all prognostic factors. Patients with HER-2 positivity in both primary and metastatic tissues (+/+) had the poorest survival (OS, 12.5 months; DFS, 11.0 months) (P < 0.01).

Conclusions

HER-2 was significantly overexpressed in gastric cancer versus normal tissue and correlated with VEGF expression. HER-2 in tumor or lymph nodes was an independent negative prognostic factor.

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Acknowledgments

This work was supported by grants from Jiangsu Provincial Natural Science Foundation (NO. BK2008477), Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education Ministry 2009 (IA09), Open Project Program of the Health Bureau of Jiangsu Province (XK18 200904), the Six Project of Jiangsu Province under Grant “Innovation Project of Jiangsu Province,” the Jiangsu Province Foundation for Key Medical Persons (RC2011053), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

Conflict of interest

The authors declare that they have no competing interests.

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Correspondence to Yongfeng Shao or Yongmei Yin.

Additional information

Y. Geng and X. Chen contributed equally to this work.

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Geng, Y., Chen, X., Qiu, J. et al. Human epidermal growth factor receptor-2 expression in primary and metastatic gastric cancer. Int J Clin Oncol 19, 303–311 (2014). https://doi.org/10.1007/s10147-013-0542-9

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  • DOI: https://doi.org/10.1007/s10147-013-0542-9

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