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World Journal of Surgery
Published in: World Journal of Surgery 10/2009

01-10-2009

Comparative Study on Overexpression of HER2/neu and HER3 in Gastric Cancer

Published in: World Journal of Surgery | Issue 10/2009

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Abstract

Background

Owing to the special importance of the HER family in tumorigenesis, the downstream signaling pathways and effectors have become the key molecules in the strategy of carcinoma-targeted therapy. Recent evidence that HER3 is responsible for tumor resistance to therapeutic agents targeting EGFR or HER2/neu, along with the new findings that HER3 is involved in the process of dedifferentiation of gastric cancer (GC) have highlighted the critical role of HER3 in cancer research. HER3 is becoming a new targeted molecule in cancer treatment. Here, we comparatively investigated the expression of HER2/neu and HER3 in gastric cancer of two pathologic types (intestinal type and diffuse type) using immunohistochemistry (IHC) and analyzed the correlation between overexpression of HER2 and HER3 and clinicopathologic parameters.

Methods

An IHC study for HER2 and HER3 was performed on 102 formalin-fixed, paraffin-embedded specimens of GC—60 intestinal and 42 diffuse types. The correlation between overexpression of HER2 and HER3 and clinicopathologic parameters was statistically analyzed.

Results

In the GC group, overexpression of HER2 and HER3 was detected in 19 (18.6%) and 14 (13.7%) of 102 GC patients, respectively. In a nontumorous group of 102 specimens, 5 were HER2-positive (4.9%) (18.6% vs. 4.9%, p < 0.01), and 2 were HER3-positive (2.0%) (13.7% vs. 2.0%, p < 0.01). No co-overexpression of HER2 and HER3 was observed. The intestinal type of GC exhibited a higher rate of HER2 overexpression than did the diffuse type (26.7% vs. 7.1%, p < 0.05), whereas the diffuse type of GC exhibited a significantly higher rate of HER3 overexpression than did the intestinal type (26.2% vs. 5.0%, p < 0.01). The overexpression rates of HER2 and HER3 in phase III–IV (TNM stage) disease were significantly higher than that in phase I–II disease (24.0% vs. 7.7%, p < 0.05 and 22.0% vs. 5.8%, p < 0.05, respectively). HER2 and HER3 overexpression was also correlated with a significantly worse survival (p = 0.046 and 0.024, respectively).

Conclusions

The selective overexpression of HER2 and HER3 in the two histologic types of gastric cancer is strongly associated with a poor prognosis. Being an important member of the HER family, HER3 may become another candidate for molecular-targeted therapy in gastric cancer, especially for the diffuse histologic type.
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Metadata
Title
Comparative Study on Overexpression of HER2/neu and HER3 in Gastric Cancer
Publication date
01-10-2009
Published in
World Journal of Surgery / Issue 10/2009
Print ISSN: 0364-2313
Electronic ISSN: 1432-2323
DOI
https://doi.org/10.1007/s00268-009-0142-z

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