title: Epithelial dysplasia of the stomach with gastric immunophenotype shows features of biological aggressiveness.
abstract: BACKGROUND
  Gastric dysplasia is classified as adenomatous/type I (intestinal phenotype) and foveolar or pyloric/type II (gastric phenotype) according to morphological (architectural and cytological) features. The immunophenotypic classification of dysplasia, based on the expression of the mucins, CD10 and CDX2, recognizes the following immunophenotypes: intestinal (MUC2, CD10, and CDX2); gastric (MUC5AC and/or MUC6, absence of CD10, and absent or low expression of CDX2); hybrid (gastric and intestinal markers); and null.
  
  
  METHODS
  Sixty-six cases of nonpolypoid epithelial dysplasia of the stomach were classified according to morphological features (histotype and grade) and immunophenotype. Immunohistochemical staining was performed with antibodies against MUC2, MUC5AC, MUC6, CD10, CDX2, chromogranin, synaptophysin, Ki-67, and TP53. HER2 alterations were analyzed by immunohistochemistry and silver-enhanced in situ hybridization.
  
  
  RESULTS
  By conventional histology, dysplasia was classified as adenomatous/intestinal (n = 42; 64 %) and foveolar or pyloric/gastric (n = 24; 36 %) and graded as low grade (n = 37; 56 %) or high grade (n = 29; 44 %). Immunophenotypic classification showed intestinal (n = 22; 33.3 %), gastric (n = 25; 37.9 %), hybrid (n = 17; 25.8 %), or null (n = 2; 3.0 %) phenotypes. In 20 cases a coexistent intramucosal carcinoma was identified. The intestinal immunophenotype was shown to be significantly associated with low-grade dysplasia (p = 0.001), high expression of CDX2 (p = 0.015), TP53 (p = 0.034), synaptophysin (p = 0.003), and chromogranin (p < 0.0001); the gastric immunophenotype was significantly associated with high-grade dysplasia (p = 0.001), high Ki-67 proliferative index (p = 0.05), and coexistence of intramucosal carcinoma (p = 0.013). HER2 amplification was observed in 3 cases, typed as gastric or hybrid.
  
  
  CONCLUSIONS
  Epithelial nonpolypoid dysplasia of the stomach with gastric immunophenotype shows features of biological aggressiveness and may represent the putative precursor lesion in a pathway of gastric carcinogenesis originated de novo from the native gastric mucosa, leading to gastric-type adenocarcinoma.
authors.affiliation: Faculty of Medicine of the University of Porto, Porto, Portugal. pedrofmvalente@gmail.com.
authors.forename: Pedro
authors.initials: P
authors.lastname: Valente
authors.affiliation: Faculty of Medicine of the University of Porto, Porto, Portugal.
authors.forename: Mónica
authors.initials: M
authors.lastname: Garrido
authors.affiliation: Faculty of Medicine of the University of Porto, Porto, Portugal.|Faculty of Medicine and Surgery, University of Genova, Genova, Italy.
authors.forename: Irene
authors.initials: I
authors.lastname: Gullo
authors.affiliation: Centro Hospitalar de São João, Porto, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Baldaia
authors.affiliation: Centro Hospitalar de São João, Porto, Portugal.
authors.forename: Margarida
authors.initials: M
authors.lastname: Marques
authors.affiliation: Centro Hospitalar de São João, Porto, Portugal.|Department of Gastroenterology and Hepatology, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Francisco
authors.initials: F
authors.lastname: Baldaque-Silva
authors.affiliation: Centro Hospitalar de São João, Porto, Portugal.
authors.forename: Joanne
authors.initials: J
authors.lastname: Lopes
authors.affiliation: Faculty of Medicine of the University of Porto, Porto, Portugal. fcarneiro@ipatimup.pt.|Centro Hospitalar de São João, Porto, Portugal. fcarneiro@ipatimup.pt.|Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Rua Dr. Roberto Frias S/N, 4200-465, Porto, Portugal. fcarneiro@ipatimup.pt.
authors.forename: Fátima
authors.initials: F
authors.lastname: Carneiro
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D011230:Precancerous Conditions / Q000473:pathology*; D013272:Stomach Diseases / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor
keywords: Dysplasia; Gastric carcinogenesis; HER2; Immunophenotype; Mucins