title: HER2 Genetic Heterogeneity in Gastric Cancer: Evaluation According to the College of American Pathologists Breast Cancer Criteria.
abstract: Gastric and gastroesophageal junction (GEJ) adenocarcinomas have been shown to display significant HER2 genetic heterogeneity (GH). This is typically seen as a cluster of HER2-positive cells but can also take the form of intermingled cells, referred to a "mosaic" pattern. GH is not well defined in gastric/GEJ tumors and the "mosaic" pattern has never been studied. We sought to evaluate the frequency and distribution of the "mosaic" pattern of GH in gastric/GEJ tumors using the College of American Pathologists-endorsed breast criteria of 5% to <50% amplified nuclei. We also postulated that the lower limit of this GH definition might be seen by chance in normal gastric epithelium. A total of 360 consecutive gastric/GEJ tumors were tested for HER2 by immunohistochemistry and in situ hybridization. Individual tumor cell HER2:CEP17 ratios were calculated for each case and the percentage of tumor cells with a ratio ≥2.0 determined. In addition, 300 normal gastric epithelial cells were scored for HER2 and CEP17 signals. Overall, 265 cases (73.4%) showed GH. The percentage of amplified cells in GH cases linearly correlated with the overall HER2:CEP17 ratio. In normal gastric epithelium, a cell with an "amplified" 2:1 ratio was seen in 9.7% (29/300) of cells, thus reaching GH. The chance of "GH" in scoring 20 normal epithelial cells was 87%. We conclude that GH is very common in gastric/GEJ tumors when College of American Pathologists breast criteria are applied and the lower threshold is likely of little clinical significance due to the finding "amplified" 2:1 nuclei in normal cells.
authors.affiliation: St. Michael's Hospital, Department of Laboratory Medicine, Li Ka Shing Knowledge Institute and the University of Toronto, ON, Canada.
authors.forename: Ann D
authors.initials: AD
authors.lastname: Treacy
authors.forename: Jason R
authors.initials: JR
authors.lastname: Karamchandani
authors.forename: Catherine J
authors.initials: CJ
authors.lastname: Streutker
authors.forename: Andrea
authors.initials: A
authors.lastname: Grin
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002503:Centromere / Q000235:genetics / Q000473:pathology; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D004938:Esophageal Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004943:Esophagogastric Junction / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D018740:Genetic Heterogeneity; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D017410:Practice Guidelines as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014314:Trisomy / Q000235:genetics* / Q000473:pathology
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human