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. 2014 Dec 16:8:7-14.
doi: 10.2147/OTT.S70922. eCollection 2015.

Assessment and prognostic analysis of EGFR, HER2, and HER3 protein expression in surgically resected gastric adenocarcinomas

Daoqiang Tang  1 , Charles Yj Liu  2 , Danping Shen  3 , Shuqiong Fan  2 , Xinying Su  2 , Peng Ye  2 , Paul R Gavine  2 , Xiaolu Yin  2
Affiliations

Assessment and prognostic analysis of EGFR, HER2, and HER3 protein expression in surgically resected gastric adenocarcinomas

Daoqiang Tang et al. Onco Targets Ther. .

Abstract

Aim: To investigate the significance of epidermal growth factor receptor (EGFR), human epidermal growth factor receptor (HER)2, and HER3 expression on survival outcomes in Chinese gastric cancer patients.

Materials and methods: Formalin-fixed, paraffin-embedded specimens from 121 patients who underwent gastrectomy at Shanghai Renji Hospital from 2007-2010 were retrospectively examined. Fluorescence in situ hybridization and immunohistochemistry techniques were used to identify gene amplification and protein overexpression. Correlations between the expression or amplification of HER family genes and clinicopathological parameters were then determined using statistical analysis.

Results: EGFR protein overexpression, an increase in HER2 copy number and gene amplification, and HER3 protein overexpression were identified in 33.1%, 17.4%, and 62.0% of samples, respectively. Statistical analysis showed a significant association between EGFR expression and tumor invasion depth or tumor stage. HER2 was also shown to be significantly associated with the tumor grade. In addition, EGFR protein overexpression was found to be significantly associated with worse overall survival (P=0.03).

Conclusion: The HER family members showed a high expression in gastric cancer. EGFR protein expression was associated with overall survival.

Keywords: clinicopathologic significance; fluorescence in situ hybridization; gastric cancer; immunohistochemistry.

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Figures

Figure 1
Figure 1
Representative image showing epidermal growth factor receptor protein expression in gastric cancer samples. Notes: (A) Immunonegativity; (B) 1+ reactivity intensity; (C) 2+ reactivity intensity; (D) 3+ reactivity intensity; (E–H) representative hematoxylin and eosin staining images for samples in (A–D), respectively (original magnification ×200).
Figure 2
Figure 2
Representative image showing human epidermal growth factor receptor 2 protein expression and gene amplification in gastric cancer samples. Notes: (A) Immunonegativity; (B) 1+ reactivity intensity; (C) 2+ reactivity intensity; (D) 3+ reactivity intensity; (E) FISH positive; (F) FISH negative; (G–J) representative hematoxylin and eosin staining images for samples in (A–D), respectively (original magnification ×200). Abbreviation: FISH, fluorescence in situ hybridization.
Figure 3
Figure 3
Representative image showing human epidermal growth factor receptor 3 protein expression in gastric cancer samples. Notes: (A) Immunonegativity; (B) 1+ reactivity intensity; (C) 2+ reactivity intensity; (D) 3+ reactivity intensity; (E–H) representative hematoxylin and eosin staining images for samples in (A–D), respectively (original magnification ×200).
Figure 4
Figure 4
An illustration of the coexpression of HER family members in gastric adenocarcinoma. Abbreviations: n, number; HER, human epidermal growth factor receptor; EGFR, epidermal growth factor receptor.
Figure 5
Figure 5
Association between patient overall survival and the overexpression of HER family members. Notes: (A) EGFR overexpression was significantly associated with worse survival (P=0.03; log-rank test). (B) No significant relationship was found between HER2 and overall survival (P=0.71). (C) No significant relationship was found between HER2 and overall survival (P=0.84). (D) Co-overexpression of EGFR and HER3 was related to worse survival, although with a boundary significance (P=0.07). (E) No significant relationship was found between overall survival and co-overexpression of EGFRand HER2 (P=0.49). (F) No significant relationship was found between overall survival and co-overexpression of HER2 and HER3 (P=0.98). All results were obtained after standardizing chemotherapy status. Abbreviations: EGFR, epidermal growth factor receptor; HER, human epidermal growth factor receptor.
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