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Evaluation of serum HER2-ECD levels in patients with gastric cancer

  • Original Article—Alimentary Tract
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An Erratum to this article was published on 21 May 2014

An Editorial to this article was published on 14 May 2014

Abstract

Background

Determination of the human epidermal growth factor receptor 2 (HER2) status of gastric cancer patients is indispensable in clinical practice. However, the clinical value of serum HER2-extracellular domain (ECD) in gastric cancer has not yet been defined.

Methods

The serum level of HER2-ECD was measured using the chemiluminescence immunoassay method, and its relationship with tissue HER2 status and clinicopathologic features was examined. Transition of serum HER2-ECD level was examined in patients during chemotherapy to clarify the correlation between changes in the level of HER2-ECD in serum and response to chemotherapy.

Results

A total of 150 gastric cancer patients were enrolled in this study; changes in HER2-ECD level were examined in 36 of these patients during chemotherapy. Serum levels of HER2-ECD ranged from 4.8 to 180.0 ng/ml (median 9.2 ng/ml) and were positive (cutoff value 15.2 ng/ml) in ten patients (6.7 %). There was a significant correlation between serum HER2-ECD level and tissue HER2 status (P < 0.001); however, no correlation with TNM stage was found. Change in serum HER2-ECD level during chemotherapy was significantly correlated with response to chemotherapy in patients with HER2-positive tumor tissue.

Conclusions

Serum HER2-ECD is a potential biomarker of gastric cancer and could be used as a diagnostic marker with regard to tissue HER2 status, and also as a monitoring marker in relation to response to chemotherapy.

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Abbreviations

HER2:

Human epidermal growth factor receptor 2

ToGA:

Trastuzumab for gastric cancer

IHC:

Immunohistochemistry

FISH:

Fluorescence in situ hybridization

ECD:

Extracellular domain

CT:

Computed tomography

PR:

Partial response

SD:

Stable disease

PD:

Progressive disease

CLIA:

Chemiluminescence immunoassays

ELISA:

Enzyme-linked immunosorbent assays

References

  1. Slamon DJ, Clark GM, Wong SG, et al. Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science. 1987;235:177–82.

    Article  CAS  PubMed  Google Scholar 

  2. Cohen JA, Weiner DB, More KF, et al. Expression pattern of the neu (NGL) gene-encoded growth factor receptor protein (p185neu) in normal and transformed epithelial tissues of the digestive tract. Oncogene. 1989;4:81–8.

    CAS  PubMed  Google Scholar 

  3. Williams TM, Weiner DB, Greene MI, et al. Expression of c-erbB-2 in human pancreatic adenocarcinomas. Pathobiology. 1991;59:46–52.

    Article  CAS  PubMed  Google Scholar 

  4. Boku N. HER2-positive gastric cancer. Gastric Cancer. 2014; 17:1–12.

    Google Scholar 

  5. Tanner M, Hollmen M, Junttila TT, et al. Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab. Ann Oncol. 2005;16:273–8.

    Article  CAS  PubMed  Google Scholar 

  6. Terashima M, Ochiai A, Kitada K, et al. Impact of human epidermal growth factor receptor (EGFR) and ERBB2 (HER2) expressions on survival in patients with stage II/III gastric cancer, enrolled in the ACTS-GC study. J Clin Oncol. 2011;29:abstract 4013.

    Google Scholar 

  7. Bang YJ, Van Cutsem E, Feyereislova A, ToGA Trial Investigators, et al. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010;376:687–97.

    Article  CAS  PubMed  Google Scholar 

  8. Wolff AC, Hammond ME, Schwartz JN, et al. American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol. 2007;25:118–45.

    Article  CAS  PubMed  Google Scholar 

  9. Hofmann M, Stoss O, Shi D, et al. Assessment of a HER2 scoring system for gastric cancer: results from a validation study. Histopathology. 2008;52:797–805.

    Article  CAS  PubMed  Google Scholar 

  10. Lam L, McAndrew N, Yee M, et al. Challenges in the clinical utility of the serum test for HER2 ECD. Biochim Biophys Acta. 2012;1826:199–208.

    CAS  PubMed Central  PubMed  Google Scholar 

  11. Ludovini V, Gori S, Colozza M, et al. Evaluation of serum HER2 extracellular domain in early breast cancer patients: correlation with clinicopathological parameters and survival. Ann Oncol. 2008;19:883–90.

    Article  CAS  PubMed  Google Scholar 

  12. Sugano K, Ushiama M, Fukutomi T, et al. Combined measurement of the c-erbB-2 protein in breast carcinoma tissues and sera is useful as a sensitive tumor marker for monitoring tumor relapse. Int J Cancer. 2000;89:329–36.

    Article  CAS  PubMed  Google Scholar 

  13. Greene FLPD, Fleming ID. American Joint Committee on cancer staging manual. 6th ed. Philadelphia: Springer; 2002.

    Book  Google Scholar 

  14. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  CAS  PubMed  Google Scholar 

  15. Narita T, Seshimo A, Suzuki M, et al. Status of tissue expression and serum levels of HER2 in gastric cancer patients in Japan. Hepatogastroenterology. 2013;60:1083–8.

    Google Scholar 

  16. Kono K, Naganuma H, Sekikawa T, et al. Serum level of HER-2/neu in patients with gastric cancer: correlation with HER-2/neu overexpression in gastric carcinoma tissue. Tumour Biol. 2000;21:139–44.

    Article  CAS  PubMed  Google Scholar 

  17. Takehana T, Kunitomo K, Kono K, et al. Status of c-erbB-2 in gastric adenocarcinoma: a comparative study of immunohistochemistry, fluorescence in situ hybridization and enzyme-linked immuno-sorbent assay. Int J Cancer. 2002;98:833–7.

    Article  CAS  PubMed  Google Scholar 

  18. Albarello L, Pecciarini L, Doglioni C. HER2 testing in gastric cancer. Adv Anat Pathol. 2011;18:53–9.

    Article  CAS  PubMed  Google Scholar 

  19. Witzel I, Loibl S, Minckwitz GV. Monitoring serum HER2 levels during neoadjuvant trastuzumab treatment within the GeparQuattro trial. Breast Cancer Res Treat. 2010;123:437–45.

    Article  CAS  PubMed  Google Scholar 

  20. Zidan J, Dashkovsky I, Stayerman C, et al. Comparison of HER-2 overexpression in primary breast cancer and metastatic sites and its effect on biological targeting therapy of metastatic disease. Br J Cancer. 2005;932:552–6.

    Article  Google Scholar 

  21. Asgeirsson KS, Agrawal A, Allen C, et al. Serum epidermal growth factor receptor and HER2 expression in primary and metastatic breast cancer patients. Breast Cancer Res. 2007;9:R75.

    Article  PubMed Central  PubMed  Google Scholar 

  22. Shimada H, Noie T, Ohashi M, et al. Clinical significance of serum tumor markers for gastric cancer: a systematic review of literature by the Task Force of the Japanese Gastric Cancer Association. Gastric Cancer. 2014;17:26–33.

    Article  CAS  PubMed  Google Scholar 

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Conflict of interests

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterologic Surgery, Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa, 920-8641, Japan

    Katsunobu Oyama, Sachio Fushida, Tomoya Tsukada, Jun Kinoshita, Toshifumi Watanabe, Masatoshi Shoji, Shinichi Nakanuma, Koichi Okamoto, Seisho Sakai, Isamu Makino, Keishi Nakamura, Hironori Hayashi, Masafumi Inokuchi, Hisatoshi Nakagawara, Tomoharu Miyashita, Hidehiro Tajima, Hiroyuki Takamura, Itasu Ninomiya, Hirohisa Kitagawa, Takashi Fujimura & Tetsuo Ohta

  2. Department of Molecular and Cellular Pathology, Kanazawa University, Kanazawa, Ishikawa, 920-8641, Japan

    Ryousuke Tajiri & Akishi Ooi

Authors
  1. Katsunobu Oyama
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  2. Sachio Fushida
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  3. Tomoya Tsukada
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  16. Hidehiro Tajima
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  18. Itasu Ninomiya
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  21. Ryousuke Tajiri
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  22. Akishi Ooi
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  23. Tetsuo Ohta
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Corresponding author

Correspondence to Sachio Fushida.

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Oyama, K., Fushida, S., Tsukada, T. et al. Evaluation of serum HER2-ECD levels in patients with gastric cancer. J Gastroenterol 50, 41–45 (2015). https://doi.org/10.1007/s00535-014-0941-3

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  • DOI: https://doi.org/10.1007/s00535-014-0941-3

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