title: Clinical Significance of HER2 Overexpression in Gastric and Gastroesophageal Junction Cancers.
abstract: BACKGROUND
  In this study, we investigated the rate of human epidermal growth factor receptor 2 (HER2) overexpression in gastric (GC) and gastroesophageal junction cancers (GEJCs) and the relationship with HER2 expression and clinical, pathological parameters and prognosis.
  
  
  METHODS
  Surgery or biopsy specimen of 598 (436 males, 162 females) patients with GC or GEJC was evaluated for the presence of HER2 overexpression by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods.
  
  
  RESULTS
  HER2 IHC scores were as follows: 418 (69.9%) IHC 0, 58 (9.7%) IHC 1+, 50 (8.4%) IHC 2+, 72 (12%) IHC 3+. Among 50 patients with IHC 2+, 18 (38.2%) were FISH positive, and 29 (61.7%) were FISH negative for HER2 amplification. Patients were regarded as HER2 positive in case of IHC 3+ disease or IHC 2+ disease with a positive FISH test result for HER2 amplification. In the primary analysis population, 90 (15%) were considered HER2 positive. HER2 positivity was higher in intestinal GC compared to diffuse GC (16.9 vs 6.6%, p = 0.014). HER2 positivity was significantly higher in well and moderately differentiated tumors than poorly differentiated tumors (p < 0.0001). HER2 positivity had no significant effect on median OS (23.2 vs 19.1 months, p = 0.44). But in the early stages (stages I and II), median OS of HER2-positive patients was shorter than HER2-negative patients (51.4 months vs not reach, p = 0.047). However, median OS was similar in patients with advanced stages (stages III and IV) HER2-positive and HER2-negative disease (16.2 vs 13.7 months, p = 0.72).
  
  
  CONCLUSIONS
  Rate of HER2 positivity is similar in Turkish patients with GC and GEJCs. HER2 positivity is associated with poor prognosis in patients with early-stage disease.
authors.affiliation: Department of Medical Oncology, Sakarya University Training and Research Hospital, Sakarya, Turkey, meltembaykara@yahoo.com.
authors.forename: Meltem
authors.initials: M
authors.lastname: Baykara
authors.forename: Mustafa
authors.initials: M
authors.lastname: Benekli
authors.forename: Ozgur
authors.initials: O
authors.lastname: Ekinci
authors.forename: Sultan Cigdem
authors.initials: SC
authors.lastname: Irkkan
authors.forename: Halit
authors.initials: H
authors.lastname: Karaca
authors.forename: Umut
authors.initials: U
authors.lastname: Demirci
authors.forename: Muhammed Bulent
authors.initials: MB
authors.lastname: Akinci
authors.forename: Olcun Umit
authors.initials: OU
authors.lastname: Unal
authors.forename: Faysal
authors.initials: F
authors.lastname: Dane
authors.forename: Fatma Paksoy
authors.initials: FP
authors.lastname: Turkoz
authors.forename: Ozan
authors.initials: O
authors.lastname: Balakan
authors.forename: Eylem Pinar
authors.initials: EP
authors.lastname: Eser
authors.forename: Selcuk Cemil
authors.initials: SC
authors.lastname: Ozturk
authors.forename: Metin
authors.initials: M
authors.lastname: Ozkan
authors.forename: Berna
authors.initials: B
authors.lastname: Oksuzoglu
authors.forename: Alper
authors.initials: A
authors.lastname: Sevinc
authors.forename: Necla
authors.initials: N
authors.lastname: Demir
authors.forename: Hakan
authors.initials: H
authors.lastname: Harputluoglu
authors.forename: Bulent
authors.initials: B
authors.lastname: Yalcin
authors.forename: Ugur
authors.initials: U
authors.lastname: Coskun
authors.forename: Aytug
authors.initials: A
authors.lastname: Uner
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ozet
authors.forename: Suleyman
authors.initials: S
authors.lastname: Buyukberber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004943:Esophagogastric Junction; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D015996:Survival Rate; D055815:Young Adult
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human