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Effect of EGFR and p-AKT Overexpression on Chromosomal Instability in Gastric Cancer

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Molecular profiling in gastric cancer (GC) is important for diagnosis and treatment. In this study, we investigated signal transduction pathways that might induce chromosomal instability in GC.

Methods

Epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), and p-AKT expression were analyzed using immunohistochemistry, and chromosomal instability was assessed by DNA aneuploidy using laser scanning cytometry, in a total of 202 GC cases.

Results

The rate of EGFR expression and p-AKT expression was 70.3 and 34.2 %, respectively, in GC patients. In total, 57.5 % of GC patients exhibited DNA aneuploidy, and p-AKT positively correlated with EGFR and HER2 (p = 0.0127 and p = 0.00031, respectively). Patients with EGFR overexpressing GC showed shorter disease-specific survival than the other cases (hazard ratio 2.00, 95 % confidence interval 1.19–3.53; p = 0.0104). Moreover, EGFR and p-AKT expression was significantly correlated with DNA aneuploidy (p = 0.0002 and p = 0.0302, respectively).

Conclusions

Our data showed that both EGFR and p-AKT overexpression were clearly associated with DNA aneuploidy. Aneuploidy could be a useful marker for therapies that target EGFR.

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Acknowledgment

The authors thank Ms. Y. Kubota for her wonderful work in preparing the IHC samples, and Ms. T. Shishino and Ms. N. Makikusa for their technical assistance.

Disclosure

Yuichi Hisamatsu, Eiji Oki, Hajime Otsu, Koji Ando, Hiroshi Saeki, Eriko Tokunaga, Shinichi Aishima, Masaru Morita, Yoshinao Oda, and Yoshihiko Maehara had no financial or personal relationships with other people or organizations that could inappropriately influence this work.

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Authors and Affiliations

  1. Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Yuichi Hisamatsu MD, PhD, Eiji Oki MD, PhD, Hajime Otsu MD, Koji Ando MD, PhD, Hiroshi Saeki MD, PhD, Eriko Tokunaga MD, PhD, Masaru Morita MD, PhD & Yoshihiko Maehara MD, PhD

  2. Department Anatomic Pathology and Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

    Shinichi Aishima MD, PhD & Yoshinao Oda MD, PhD

Authors
  1. Yuichi Hisamatsu MD, PhD
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  2. Eiji Oki MD, PhD
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  3. Hajime Otsu MD
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  4. Koji Ando MD, PhD
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  5. Hiroshi Saeki MD, PhD
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  6. Eriko Tokunaga MD, PhD
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  7. Shinichi Aishima MD, PhD
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  9. Yoshinao Oda MD, PhD
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  10. Yoshihiko Maehara MD, PhD
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Corresponding author

Correspondence to Eiji Oki MD, PhD.

Electronic Supplementary Material

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Supplementary material 1 (DOCX 28 kb).

10434_2016_5097_MOESM2_ESM.tif

Supplementary material 2 Figure 1. Immunohistochemical analysis of EGFR and p-AKT in normal gastric tissue. Representative images showing EGFR expression in gastric normal specimens (A, B). Cells were considered EGFR (A) or EGFR+ (B) according to positive immunostaining of the cell membrane. Original magnification: ×200. (TIFF 891 kb).

10434_2016_5097_MOESM3_ESM.tif

Supplementary material 3 Supplementary Figure 2. The level of EGFR expression in NCI-N87 cells. Western blotting analysis using anti-EGFR (sc-03) rabbit polyclonal antibody indicated a band at the predicted size (170 kDa) (TIFF 26 kb).

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Hisamatsu, Y., Oki, E., Otsu, H. et al. Effect of EGFR and p-AKT Overexpression on Chromosomal Instability in Gastric Cancer. Ann Surg Oncol 23, 1986–1992 (2016). https://doi.org/10.1245/s10434-016-5097-3

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  • DOI: https://doi.org/10.1245/s10434-016-5097-3

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