title: HER Family Protein Expression in a Greek Population with Gastric Cancer. A Retrospective Hellenic Cooperative Oncology Group Study.
abstract: BACKGROUND
  Gastric cancer is a relatively common malignancy. Recently, the presence of the human epidermal growth factor receptor 2 (HER2) was identified as a molecular target in a proportion of patients who benefited from the addition of appropriate anti-HER2 treatments. Our study explored the clinical and prognostic role of known HER family members, human epidermal growth factor receptor 1 (EGFR or HER1), HER2, HER3 and HER4.
  
  
  METHODS
  Formalin-fixed paraffin-embedded (FFPE) tumor tissue samples from 249 gastric cancer patients were studied by immunohistochemistry for protein expression of EGFR, HER2, HER3 and HER4.
  
  
  RESULTS
  Of the 249 evaluable patients, 32 did not have complete data of treatment details and/or follow-up and were excluded from the survival analyses. Of the 217 patients with complete treatment and follow-up data, 178 were operated and treated for early disease (group 1), while 39 for advanced disease (group 2). The frequency of positive EGFR, HER2, HER3 and HER4 protein expression in all patients was 17.5%, 11.8%, 14.8% and 32.9%, respectively. There were no differences in protein expression of any of the markers between the two groups. There were, however, statistically significant associations between HER4 and all other HER family members, as well as between HER2 and HER3 expression. Of note, EGFR-positive membranous protein expression was significantly associated with the presence of lymphovascular invasion (p=0.027) and HER3 and HER4 negative cytoplasmic protein expression with well/moderately-differentiated tumors (p=0.030 and p=0.014, respectively). None of the HER family members were of prognostic value for OS in univariate analysis.
  
  
  CONCLUSIONS
  The present study confirmed the known protein expression frequencies of HER family members in gastric cancer in a Greek population. Several associations were observed among the HER family members and between clinicopathological characteristics and HER family members. Further research is needed on their exact prognostic role, as well as their therapeutic targeting.
authors.affiliation: Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece maktom@yahoo.com.
authors.forename: Thomas
authors.initials: T
authors.lastname: Makatsoris
authors.affiliation: Department of Pathology, University Hospital, University of Patras Medical School, Patras, Greece.
authors.forename: Athanassios C
authors.initials: AC
authors.lastname: Tsamandas
authors.affiliation: Fourth Oncology Unit, Euroclinic Athens Hospital, Athens, Greece.
authors.forename: Alexios
authors.initials: A
authors.lastname: Strimpakos
authors.affiliation: Department of Biostatistics, Health Data Specialists Ltd, Athens, Greece.
authors.forename: Zoi
authors.initials: Z
authors.lastname: Alexopoulou
authors.affiliation: Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Dionysopoulos
authors.affiliation: Department of Pathology, "Papageorgiou" Hospital, Thessaloniki, Greece.
authors.forename: Stavroula
authors.initials: S
authors.lastname: Pervana
authors.affiliation: Department of Surgery, St. Luke's Hospital, Thessaloniki, Greece.
authors.forename: Athina
authors.initials: A
authors.lastname: Konstantara
authors.affiliation: Oncology Unit, "Hippokration" Hospital, Athens, Greece.
authors.forename: Pavlos
authors.initials: P
authors.lastname: Papakostas
authors.affiliation: Third Department of Medical Oncology, "Agii Anargiri" Cancer Hospital, Athens, Greece.
authors.forename: Epaminontas
authors.initials: E
authors.lastname: Samantas
authors.affiliation: Department of Medical Oncology, "Papageorgiou" Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece.
authors.forename: Grigoris
authors.initials: G
authors.lastname: Rallis
authors.affiliation: Yale Cancer Center, Yale School of Medicine, New Haven, CT, U.S.A.
authors.forename: Anastasios
authors.initials: A
authors.lastname: Dimou
authors.affiliation: Department of Medical Oncology, Ioannina University Hospital, Ioannina, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Pentheroudakis
authors.affiliation: Department of Pathology, General Hospital Konstantopouleio Agia Olga, Athens, Greece.
authors.forename: Kleo
authors.initials: K
authors.lastname: Papaparaskeva
authors.affiliation: Division of Oncology, Second Department of Internal Medicine, Attikon University Hospital, Athens, Greece.
authors.forename: Amanda
authors.initials: A
authors.lastname: Psyrri
authors.affiliation: Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece Translational Research Section, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece.
authors.forename: Konstantine T
authors.initials: KT
authors.lastname: Kalogeras
authors.affiliation: Yale Cancer Center, Yale School of Medicine, New Haven, CT, U.S.A.
authors.forename: Kostas
authors.initials: K
authors.lastname: Syrigos
authors.affiliation: Department of Pathology, University Hospital, University of Patras Medical School, Patras, Greece.
authors.forename: Chrisoula D
authors.initials: CD
authors.lastname: Scopa
authors.affiliation: Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece Aristotle University of Thessaloniki, Thessaloniki, Greece.
authors.forename: George
authors.initials: G
authors.lastname: Fountzilas
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D006115:Greece / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000378:metabolism*; D055815:Young Adult
chemical_list: D066246:ErbB Receptors
keywords: EGF family of proteins; Stomach; adenocarcinoma; immunohistochemistry