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Open AccessArticle

Trastuzumab Specific Epitope Evaluation as a Predictive and Prognostic Biomarker in Gastric Cancer Patients

1
Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 110-744, Korea
2
Department of Pathology, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si 13488, Korea
3
Department of Nuclear Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si 13488, Korea
4
Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si 13488, Korea
5
Department of Internal Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 110-744, Korea
6
Department of Surgery, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam-si 13488, Korea
7
Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, Seoul 110-744, Korea
*
Authors to whom correspondence should be addressed.
Biomolecules 2019, 9(12), 782; https://doi.org/10.3390/biom9120782
Received: 11 October 2019 / Revised: 23 November 2019 / Accepted: 25 November 2019 / Published: 26 November 2019
(This article belongs to the Special Issue Advances in Antibody Therapy of Cancer)
While human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) antibodies bind to the intracellular domain, trastuzumab binds to the extracellular epitope of HER2 receptor: target of drug action. We aimed to evaluate clinical significance of the new IHC method assessing the target of trastuzumab in gastric cancer (GC) patients and compare with conventional methods. Sixty-nine trastuzumab-treated GC patients were enrolled from two different cohorts. Additionally, we enrolled 528 consecutive GC patients to evaluate prognostic implications of HER2 test methods. HER2 status was assessed by trastuzumab IHC, HER2 IHC (4B5), and HER2 silver in situ hybridization (SISH). HER2 IHC showed 3+ in 48/69 trastuzumab-treated patients (69.6%), however, trastuzumab IHC showed 3+ in 25 (36.2%). Patients with trastuzumab IHC ≥2+ had significantly better progression-free survival (PFS) and overall survival (OS) than their counterpart (p = 0.014). In univariate analysis, trastuzumab IHC ≥2+ and HER2 IHC 3+ were only significant predictive factors for OS in trastuzumab-treated patients. Of the 528 consecutive GCs, patients with trastuzumab IHC ≥2+ had shorter disease-free survival (DFS) and OS (p = 0.008 and 0.031, respectively), while conventional methods failed to reveal any significant survival differences. HER2 assessment by trastuzumab IHC was different from conventional HER2 test results. Trastuzumab IHC was suggested to be a significant predictive factor for trastuzumab responsiveness and prognostic factor for consecutive GCs. View Full-Text
Keywords: trastuzumab; HER2; gastric cancer; prognosis; prediction trastuzumab; HER2; gastric cancer; prognosis; prediction
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Koh, J.; Nam, S.K.; Lee, Y.W.; Kim, J.W.; Lee, K.-W.; Ock, C.-Y.; Oh, D.-Y.; Ahn, S.-H.; Kim, H.-H.; Kang, K.-W.; Kim, W.H.; Lee, H.-Y.; Lee, H.S. Trastuzumab Specific Epitope Evaluation as a Predictive and Prognostic Biomarker in Gastric Cancer Patients. Biomolecules 2019, 9, 782.

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