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HER2 Expression in Carcinomas of the True Cardia (Siewert Type II Esophagogastric Junction Carcinoma)

World Journal of Surgery volume 38, pages 426–430 (2014)Cite this article

Abstract

Objectives

To evaluate the HER2 status in patients with Siewert type II esophagogastric junction carcinoma.

Background

Trastuzumab is now approved for use in the treatment of human epidermal growth factor receptor 2 (HER2)-positive unresectable metastatic gastric or esophagogastric junction (EGJ) carcinoma. Several studies have evaluated HER2 status in EGJ carcinoma, but none has addressed the implication of HER2 positivity in patients with Siewert type II EGJ carcinoma.

Methods

We retrospectively evaluated the frequency of HER2 positivity in a large single-center cohort of 208 patients with Siewert type II tumors. The relations between HER2 expression and the outcomes and other clinicopathologic features were examined.

Results

Overall, 18.2 % (38/208) of patients in our cohort had HER2-positive tumors. HER2 positivity was associated only with differentiated carcinomas. The 5-year overall survival (OS) rate was 58.7 %. The 5-year OS rates in the patient groups with HER2-negative and HER2-positive tumors were 61.2 and 48.5 %, respectively. There was no significant difference between the groups. Recurrence in the liver was observed in 23.7 % patients of the HER2-positive group and 7.6 % patients of the HER2-negative group. Multivariate analysis to identify the risk factors for liver recurrence revealed only HER2 positivity (p = 0.0155) as an independent predictive factor.

Conclusions

HER2 positivity is a powerful predictor of liver recurrence in patients with Siewert type II EGJ carcinoma. Use of trastuzumab in combination with chemotherapy in an adjuvant setting can be a potentially useful therapeutic strategy to prevent hepatic recurrence in patients with resectable EGJ adenocarcinoma showing HER2 overexpression.

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References

  1. Bang YJ, Van Cutsem E, Feyereislova A et al (2010) 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 376:687–697

    CAS  PubMed  Article  Google Scholar 

  2. Kusano C, Gotoda T, Khor CJ et al (2008) Changing trends in the proportion of adenocarcinoma of the esophagogastric junction in a large tertiary referral center in Japan. J Gastroenterol Hepatol 23:1662–1665

    PubMed  Article  Google Scholar 

  3. Yamashita H, Katai H, Morita S et al (2011) Optimal extent of lymph node dissection for Siewert type II esophagogastric junction carcinoma. Ann Surg 254:274–280

    PubMed  Article  Google Scholar 

  4. Siewert JR, Stein HJ (1996) Carcinoma of the gastroesophageal junction: classification, pathology and extent of resection. Dis Esophagus 9:173–182

    Google Scholar 

  5. Janjigian YY, Werner D, Pauligk C et al (2012) Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA international collaborative analysis. Ann Oncol 23:2656–2662

    CAS  PubMed  Article  Google Scholar 

  6. Kataoka Y, Okabe H, Yoshizawa A et al (2013) HER2 expression and its clinicopathological features in resectable gastric cancer. Gastric Cancer 16:84–93

    CAS  PubMed  Article  Google Scholar 

  7. Gravalos C, Jimeno A (2008) HER2 in gastric cancer: a new prognostic factor and a novel therapeutic target. Ann Oncol 19:1523–1529

    CAS  PubMed  Article  Google Scholar 

  8. Bang Y, Chung J, Xu J, et al (2009) Pathological features of advanced gastric cancer (GC): relationship to human epidermal growth factor receptor 2 (HER2) positivity in the global screening programme of the ToGA trial. J Clin Oncol (Meeting Abstracts) 27(Suppl 15):abstract 4556

  9. Begnami MD, Fukuda E, Fregnani JH et al (2011) Prognostic implications of altered human epidermal growth factor receptors (HERs) in gastric carcinomas: HER2 and HER3 are predictors of poor outcome. J Clin Oncol 29:3030–3036

    CAS  PubMed  Article  Google Scholar 

  10. Kim KC, Koh YW, Chang HM et al (2011) Evaluation of HER2 protein expression in gastric carcinomas: comparative analysis of 1,414 cases of whole-tissue sections and 595 cases of tissue microarrays. Ann Surg Oncol 18:2833–2840

    PubMed  Article  Google Scholar 

  11. Ruschoff J, Hanna W, Bilous M et al (2012) HER2 testing in gastric cancer: a practical approach. Mod Pathol 25:637–650

    PubMed  Article  Google Scholar 

  12. Sobin LH, Gospodarowicz MK, Wittekind C (eds) (2009) TNM classification of malignant tumours, 7th edn. Wiley-Blackwell, Hoboken

    Google Scholar 

  13. Chua TC, Merrett ND (2012) Clinicopathologic factors associated with HER2-positive gastric cancer and its impact on survival outcomes: a systematic review. Int J Cancer 130:2845–2856

    CAS  PubMed  Article  Google Scholar 

  14. Terashima M, Kitada K, Ochiai A et al (2012) Impact of expression of human epidermal growth factor receptors EGFR and ERBB2 on survival in stage II/III gastric cancer. Clin Cancer Res 18:5992–6000

    CAS  PubMed  Article  Google Scholar 

  15. Park YS, Ryu M, Park HJ, et al (2011) HER2 status as an independent prognostic marker in patients with advanced gastric cancer receiving adjuvant chemotherapy after curative gastrectomy. J Clin Oncol (Meeting Abstracts) 29(Suppl 15):abstract 4084

  16. Park DI, Yun JW, Park JH et al (2006) HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci 51:1371–1379

    CAS  PubMed  Article  Google Scholar 

  17. Grabsch H, Sivakumar S, Gray S et al (2010) HER2 expression in gastric cancer: rare, heterogeneous and of no prognostic value—conclusions from 924 cases of two independent series. Cell Oncol 32:57–65

    PubMed  Google Scholar 

  18. Sasano H, Date F, Imatani A et al (1993) Double immunostaining for c-erbB-2 and p53 in human stomach cancer cells. Hum Pathol 24:584–589

    CAS  PubMed  Article  Google Scholar 

  19. Slamon DJ, Clark GM, Wong SG et al (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 235:177–182

    CAS  PubMed  Article  Google Scholar 

  20. Slamon DJ, Godolphin W, Jones LA et al (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707–712

    CAS  PubMed  Article  Google Scholar 

  21. Katai H, Maruyama K, Sasako M et al (1994) Mode of recurrence after gastric cancer surgery. Dig Surg 11:99–103

    Article  Google Scholar 

  22. Ishida M, Morita S, Saka M et al (2012) Metachronous liver metastasis from early gastric cancer. J Gastrointest Surg 16:837–841

    PubMed  Article  Google Scholar 

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Conflict of interest

The authors have no conflicts of interest to declare.

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Affiliations

  1. Gastric Surgery Division, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Hitoshi Katai, Michihiro Ishida, Hiroharu Yamashita, Masaki Ohashi, Shinji Morita, Hiroshi Katayama & Takeo Fukagawa

  2. Pathology Division, National Cancer Center Hospital, Tokyo, 104-0045, Japan

    Ryoji Kushima

Authors
  1. Hitoshi Katai
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  2. Michihiro Ishida
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  3. Hiroharu Yamashita
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  4. Masaki Ohashi
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  5. Shinji Morita
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  6. Hiroshi Katayama
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  7. Takeo Fukagawa
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  8. Ryoji Kushima
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Correspondence to Hitoshi Katai.

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Katai, H., Ishida, M., Yamashita, H. et al. HER2 Expression in Carcinomas of the True Cardia (Siewert Type II Esophagogastric Junction Carcinoma). World J Surg 38, 426–430 (2014). https://doi.org/10.1007/s00268-013-2256-6

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  • DOI: https://doi.org/10.1007/s00268-013-2256-6

Keywords

  • Overall Survival
  • Trastuzumab
  • Liver Recurrence
  • Siewert Type
  • Esophagogastric Junction Carcinoma