title: Association between HER2 status in gastric cancer and clinicopathological features: a retrospective study using whole-tissue sections.
abstract: BACKGROUND
  Gastric cancer is usually diagnosed in an advanced stage of disease and treatment options are sparse. Trastuzumab was recently approved for metastatic or locally advanced carcinomas arising in the stomach or in the gastroesophageal junction in patients with HER2-positive tumors. However, data on the frequency of HER2-positive cases among Brazilian patients are limited. Our aim was to characterize HER2 protein and gene status in a series of Brazilian patients with gastric cancer and to evaluate its association with clinicopathological data.
  
  
  METHODS
  Histological slides from 124 primary gastrectomies were reviewed and their pathological reports were retrieved from the files at a Brazilian university hospital. Automated immunohistochemistry for HER2 was performed on whole-tissue sections from each tumor. HER2-equivocal cases by immunohistochemistry were submitted to automated dual in situ hybridization for gene amplification evaluation. HER2 status was confronted with clinicopathological parameters in order to assess statistically significant associations.
  
  
  RESULTS
  Immunohistochemistry analysis revealed that 13/124 cases (10.5 %) were HER2 positive (3+), 10/124 cases (8.1 %) were equivocal (2+) and 101/124 cases (81.4 %) were negative, being 7 cases 1+. None of the equivocal cases showed gene amplification. The overall HER2 positivity rate was 10.5 %. There was an association between HER2 expression and Laurén's intestinal histological subtype (P = 0.048), well to moderately differentiated tumors (P = 0.004) and presence of lymphovascular invasion (P = 0.031). No association was found between HER2 status and tumor topography.
  
  
  CONCLUSIONS
  Confronted with data published by other authors, the lower percentage of HER2-positive cases found in our series might be partially explained by the lower frequency of tumors arising at the gastroesophageal junction in comparison with distal gastric carcinomas in Brazilian patients. This could also account for the lack of statistically significant association between HER2 status and tumor topography in our study.
authors.affiliation: Departamento de Medicina DEMED-UFSJ, Campus Dom Bosco. Praça Dom Helvécio, 74. Fábricas, São João del-Rei, MG, 36301-160, Brazil. renatoslab@gmail.com.
authors.forename: Renato Santos
authors.initials: RS
authors.lastname: Laboissiere
authors.affiliation: Departamento de Anatomia Patológica FM-UFMG, Avenida Prof. Alfredo Balena, 190 - 3o. andar, Belo Horizonte, MG, 30130-100, Brazil. marcelobuzelin@hotmail.com.
authors.forename: Marcelo Araújo
authors.initials: MA
authors.lastname: Buzelin
authors.affiliation: Departamento de Anatomia Patológica FM-UFMG, Avenida Prof. Alfredo Balena, 190 - 3o. andar, Belo Horizonte, MG, 30130-100, Brazil. debalabra@gmail.com.
authors.forename: Débora
authors.initials: D
authors.lastname: Balabram
authors.affiliation: Departamento de Anatomia Patológica FM-UFMG, Avenida Prof. Alfredo Balena, 190 - 3o. andar, Belo Horizonte, MG, 30130-100, Brazil. debrot@gmail.com.
authors.forename: Marina
authors.initials: M
authors.lastname: De Brot
authors.affiliation: Departamento de Anatomia Patológica FM-UFMG, Avenida Prof. Alfredo Balena, 190 - 3o. andar, Belo Horizonte, MG, 30130-100, Brazil. cristianabnunes@gmail.com.
authors.forename: Cristiana Buzelin
authors.initials: CB
authors.lastname: Nunes
authors.affiliation: Departamento de Anatomia Patológica FM-UFMG, Avenida Prof. Alfredo Balena, 190 - 3o. andar, Belo Horizonte, MG, 30130-100, Brazil. rafael.malagoli@gmail.com.
authors.forename: Rafael Malagoli
authors.initials: RM
authors.lastname: Rocha
authors.affiliation: Departamento de Anatomia Patológica FM-UFMG, Avenida Prof. Alfredo Balena, 190 - 3o. andar, Belo Horizonte, MG, 30130-100, Brazil. mgalvarescabral@hotmail.com.
authors.forename: Mônica Maria Demas Álvares
authors.initials: MM
authors.lastname: Cabral
authors.affiliation: Departamento de Anatomia Patológica FM-UFMG, Avenida Prof. Alfredo Balena, 190 - 3o. andar, Belo Horizonte, MG, 30130-100, Brazil. helenicegobbi@gmail.com.
authors.forename: Helenice
authors.initials: H
authors.lastname: Gobbi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001938:Brazil; D002277:Carcinoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D005260:Female; D005743:Gastrectomy; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology / Q000601:surgery
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human