Prognosis of metastatic gastric and gastroesophageal junction cancer by HER2 status: a European and USA International collaborative analysis.
BACKGROUND
To determine whether human epidermal growth factor receptor 2 (HER2) status is an independent prognostic factor in metastatic gastric and gastroesophageal junction (GEJ) adenocarcinoma.


METHODS
Formalin-fixed paraffin-embedded tumor samples from 381 metastatic gastric/GEJ cancer patients enrolled at Krankenhaus Nordwest and Memorial Sloan-Kettering Cancer Centers on six first-line trials of chemotherapy without trastuzumab were examined for HER2 by immunohistochemistry (IHC) and in situ hybridization (ISH). IHC 3+ or ISH-positive tumors were considered HER2 positive.


RESULTS
Seventy-eight of 381 patients (20%) had HER2-positive disease. In the multivariate logistic model, there were significantly higher rates of HER2 positivity in patients with liver metastasis (liver metastasis 31%; no liver metastasis 11%; P = 0.025) and intestinal histology (intestinal 33%; diffuse/mixed 8%; P = 0.001). No significant differences in HER2 positivity were found between resections and biopsies or primaries and metastases. Patients with HER2-positive gastric cancer had longer median overall survival compared with HER2-negative gastric cancer patients (13.9 versus 11.4 months, P = 0.047), but multivariate analysis indicated that HER2 status was not an independent prognostic factor (hazard ratio 0.79; 0.44-1.14; P = 0.194).


CONCLUSIONS
Approximately 20% of Western patients with metastatic gastric cancer are HER2 positive. Unlike breast cancer, HER2 positivity is not independently prognostic of patient outcome in metastatic gastric or GEJ.
Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College of Cornell University, New York, USA.
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Janjigian
Department of Hematology and Oncology, Institute of Clinical Research, Krankenhaus Nordwest, University Cancer Center, Frankfurt.
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D
Werner
Department of Hematology and Oncology, Institute of Clinical Research, Krankenhaus Nordwest, University Cancer Center, Frankfurt.
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C
Pauligk
Department of Hematology and Oncology, Institute of Clinical Research, Krankenhaus Nordwest, University Cancer Center, Frankfurt.
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Steinmetz
Department of Medicine, Memorial Sloan-Kettering Cancer Center, Weill Cornell Medical College of Cornell University, New York, USA.
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Kelsen
Department of Hematology and Oncology, Institute of Clinical Research, Krankenhaus Nordwest, University Cancer Center, Frankfurt.
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Jäger
Department of Pathology, Krankenhaus Nordwest, Frankfurt, Germany.
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Altmannsberger
Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA.
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Robinson
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York.
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Tafe
Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York.
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LH
Tang
Department of Medicine, Weill Cornell Medical College of Cornell University, New York, USA.
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MA
Shah
Department of Hematology and Oncology, Institute of Clinical Research, Krankenhaus Nordwest, University Cancer Center, Frankfurt. Electronic address: albatran@aol.com.
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Al-Batran
D004938:Esophageal Neoplasms / Q000378:metabolism / Q000473:pathology*; D004943:Esophagogastric Junction / Q000473:pathology*; D005060:Europe; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D009362:Neoplasm Metastasis; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014481:United States