title: Brain metastases in gastro-oesophageal adenocarcinoma: insights into the role of the human epidermal growth factor receptor 2 (HER2).
abstract: BACKGROUND
  Gastro-oesophageal adenocarcinomas rarely metastasize to the central nervous system (CNS). The role of the human epidermal growth factor receptor 2 (HER2) in patients with these cancers and CNS involvement is presently unknown.
  
  
  METHODS
  A multicentre registry was established to collect data from patients with gastro-oesophageal adenocarcinomas and CNS involvement both retrospectively and prospectively. Inclusion in the study required a predefined clinical data set, a central neuro-radiological or histopathological confirmation of metastatic CNS involvement and central assessment of HER2 by immunohistochemistry (IHC) and in situ hybridisation (ISH). In addition, expression of E-cadherin and DNA mismatch repair (MMR) proteins were assessed by IHC.
  
  
  RESULTS
  One hundred patients fulfilled the inclusion criteria. The population's median age was 59 years (interquartile range: 54-68), of which 85 (85%) were male. Twenty-five patients were of Asian and 75 of Caucasian origin. HER2 status was positive in 36% (95% CI: 26.6-46.2) of cases. Median time from initial diagnosis to the development of brain metastases (BMets) or leptomeningeal carcinomatosis (LC) was 9.9 months (95% CI: 8.5-15.0). Median overall survival from diagnosis was 16.9 months (95% CI: 14.0-20.7) and was not related to the HER2 status. E-cadherin loss was observed in 9% of cases and loss of expression in at least one DNA MMR proteins in 6%.
  
  
  CONCLUSIONS
  The proportion of a positive HER2 status in patients with gastro-oesophageal adenocarcinoma and CNS involvement was higher than expected. The impact of anti-HER2 therapies should be studied prospectively.
authors: Service d'oncologie médical, Hôpital du Valais, Sion 1951, Switzerland.|NCCCR, Hamad Medical Corporation, PO Box 3050, Doha, Qatar.
authors: J
authors: J
authors: Feilchenfeldt
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich 8091, Switzerland.
authors: Z
authors: Z
authors: Varga
authors: Department of Oncology and Hematology, Kantonsspital St Gallen, St Gallen 9700, Switzerland.
authors: M
authors: M
authors: Siano
authors: Department of Pathology, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht 6229HX, The Netherlands.
authors: H I
authors: HI
authors: Grabsch
authors: Horten Center for Patient-Oriented Research and Knowledge Transfer, University of Zurich, Zurich 8091, Switzerland.
authors: U
authors: U
authors: Held
authors: Neuroradiology, MRI Medizinisch Radiologisches Institut, Zurich 8001, Switzerland.
authors: B
authors: B
authors: Schuknecht
authors: Department of Radiation Oncology, Netherlands Cancer Institute, Amsterdam 1066, The Netherlands.
authors: A
authors: A
authors: Trip
authors: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital Tokyo, Tokyo 104-0045, Japan.
authors: T
authors: T
authors: Hamaguchi
authors: Department of Radiooncology, Luzerner Kantonsspital, Lucerne 6000, Switzerland.
authors: P
authors: P
authors: Gut
authors: Department of Pathology, Netherlands Cancer Institute, Amsterdam 1066, The Netherlands.
authors: O
authors: O
authors: Balague
authors: Department of Radiooncology, Hôpital du Valais, Sion 1951, Switzerland.
authors: K
authors: K
authors: Khanfir
authors: Institute of Pathology, Luzerner Kantonsspital, Lucerne 6000, Switzerland.
authors: J
authors: J
authors: Diebold
authors: Institute of Pathology, Kantonsspital, St Gallen 9700, Switzerland.
authors: W
authors: W
authors: Jochum
authors: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital Tokyo, Tokyo 104-0045, Japan.
authors: H
authors: H
authors: Shoji
authors: Department of Clinical Laboratory Medicine and Pathology, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192, Japan.
authors: R
authors: R
authors: Kushima
authors: Department of Oncology, CHUV, Lausanne 1011, Switzerland.
authors: D
authors: D
authors: Wagner
authors: Gastrointestinal Medical Oncology Division, National Cancer Center Hospital Tokyo, Tokyo 104-0045, Japan.
authors: Y
authors: Y
authors: Shimada
authors: Department of Gastroenterology, Netherlands Cancer Institute, Amsterdam 1066, The Netherlands.
authors: A
authors: A
authors: Cats
authors: NCCCR, Hamad Medical Corporation, PO Box 3050, Doha, Qatar.|Department of Oncology, University Hospital Zurich, Zurich 8091, Switzerland.
authors: A
authors: A
authors: Knuth
authors: Institute of Surgical Pathology, University Hospital Zurich, Zurich 8091, Switzerland.
authors: H
authors: H
authors: Moch
authors: Department of Oncology, Luzerner Kantonsspital, Lucerne 6000, Switzerland.
authors: S
authors: S
authors: Aebi
authors: Department of Oncology, University Hospital Zurich, Zurich 8091, Switzerland.|Department of Oncology, Luzerner Kantonsspital, Lucerne 6000, Switzerland.
authors: S
authors: S
authors: Hofer
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D000368:Aged; D015703:Antigens, CD; D001932:Brain Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000556:secondary; D015820:Cadherins / Q000378:metabolism; D004260:DNA Repair; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
chemical_list: D015703:Antigens, CD; D015820:Cadherins; D018719:Erb-b2 Receptor Tyrosine Kinases; C513384:CDH1 protein, human; C508053:ERBB2 protein, human