title: Discordant HER2 expression and response to neoadjuvant chemoradiotherapy in esophagogastric adenocarcinoma.
abstract: BACKGROUND
  Targeting human epidermal growth factor receptor 2 (HER2) with trastuzumab in metastatic esophagogastric adenocarcinoma (EGA) improves survival. The impact of HER2 inhibition in combination with chemoradiotherapy (CRT) in early stage EGA is under investigation. This study analyzed the pattern of HER2 overexpression in matched-pair tumor samples of patients who underwent neoadjuvant CRT followed by surgery.
  
  
  METHODS
  All patients with EGA who underwent standard neoadjuvant CRT followed by esophagectomy at the University of Florida were included. Demographics, risk factors, tumor features, and outcome data were analyzed. Descriptive statistics, Chi-square exact test, uni- and multivariate analyses, and Kaplan Meier method were used. HER2 expression determined by immunohistochemical (IHC) was scored as negative (0, 1+), indeterminate (2+) or positive (3+).
  
  
  RESULTS
  Among 49 sequential patients (41 M/8 F) with matched-pair tumor samples, 9/49 patients (18%) had pathologic complete response (pCR), 10/49 had near pCR or not enough tumor (NET) to examine in the post- treatment samples. Patients with initial HER2 negativity demonstrated conversion to HER2 positivity after neoadjuvant CRT (7/30 cases; 23%). Baseline HER2 overexpression was more common in lower stage/node negative patients (67% in stages I, IIA vs. 33% in stages IIB, III) and did not correlate with treatment response or survival.
  
  
  CONCLUSIONS
  Although limited by a relatively small sample size, our study failed to demonstrate that baseline HER2 protein over-expression in EGA predicts response to standard CRT. However, our data suggested that HER2 was up regulated by CRT resulting in unreliable concordance between pre-treatment (pre-tx) and post-treatment (post-tx) samples. Pre-therapy HER2 expression may not reliably reflect the HER2 status of persistent or recurrent disease.
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Ellie
authors.initials: E
authors.lastname: Chan
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Lizette Vila
authors.initials: LV
authors.lastname: Duckworth
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Ahmad
authors.initials: A
authors.lastname: Alkhasawneh
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Tania Zuluaga
authors.initials: TZ
authors.lastname: Toro
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Lu
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Kfir
authors.initials: K
authors.lastname: Ben-David
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Hughes
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Georgios
authors.initials: G
authors.lastname: Rossidis
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Zlotecki
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Lightsey
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Karen C
authors.initials: KC
authors.lastname: Daily
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Long
authors.initials: L
authors.lastname: Dang
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Allegra
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Brent
authors.initials: B
authors.lastname: King
authors.affiliation: 1 Division of Hematology & Oncology, Department of Medicine, University of California San Francisco, Fresno Medical Education Program, California, USA ; 2 Department of Pathology, Immunology and Laboratory Medicine, 3 Department of Biostatistics, 4 Department of Surgery, 5 Department of Radiation Oncology, 6 Division of Hematology & Oncology, Department of Medicine, University of Florida, College of Medicine, Gainesville, FL, USA.
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: George
keywords: Chemoradiation; esophagogastric adenocarcinoma (EGA); human epidermal growth factor receptor 2 (HER2)