title: Histopathological characterization of ductal carcinoma in situ (DCIS) of the breast according to HER2 amplification status and molecular subtype.
abstract: This study aimed to characterize ductal carcinoma in situ (DCIS) according to human epidermal growth factor receptor 2 (HER2) amplification status and molecular subtype. In addition, we performed a detailed HER2 and CEP17 copy number analysis and we assessed the impact of recent changes in the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines on HER2 immunohistochemical (IHC) scores in DCIS. Nuclear grade, extensive comedonecrosis, stromal architecture, stromal inflammation, and progesterone receptor (PR) expression were significantly associated with HER2 amplification status. In multivariate analysis, stromal inflammation and extensive comedonecrosis were the only two features that remained significantly related to HER2 amplification status. The recent changes in ASCO/CAP guidelines resulted in significant upgrading of HER2 IHC score. Remarkably, about one in five non-amplified DCIS presented a 3+ IHC score, regardless of the scoring method. The biological significance of this phenomenon is presently unknown. After categorization according to molecular subtype, luminal A DCIS mainly presented histopathological features associated with good prognosis, whereas luminal B/HER2+ and HER2+ categories displayed a more aggressive phenotype. Overall, our results demonstrate that HER2-amplified DCIS constitute a clearly distinct subgroup which is characterized by histopathological features associated with poor prognosis. Further studies are required to elucidate the biological significance of a 3+ IHC score in non-amplified DCIS, as well as its mechanism.
authors: Department of Pathology, Ghent University, Ghent, Belgium, Mieke.VanBockstal@UGent.be.
authors: Mieke
authors: M
authors: Van Bockstal
authors: Kathleen
authors: K
authors: Lambein
authors: Hannelore
authors: H
authors: Denys
authors: Geert
authors: G
authors: Braems
authors: Ann
authors: A
authors: Nuyts
authors: Rudy
authors: R
authors: Van den Broecke
authors: Veronique
authors: V
authors: Cocquyt
authors: Olivier
authors: O
authors: De Wever
authors: Louis
authors: L
authors: Libbrecht
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000737:chemistry / Q000235:genetics / Q000473:pathology*; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D016015:Logistic Models; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human