title: Correlation of levels and patterns of genomic instability with histological grading of DCIS.
abstract: BACKGROUND
  Histological grading of ductal carcinoma-in-situ (DCIS) lesions separates DCIS into three subgroups (well-, moderately, or poorly differentiated). It is unclear, however, whether breast disease progresses along a histological continuum or whether each grade represents a separate disease. In this study, levels and patterns of allelic imbalance (AI) were examined in DCIS lesions to develop molecular models that can distinguish pathological classifications of DCIS.
  
  
  METHODS
  Laser microdissected DNA samples were collected from DCIS lesions characterized by a single pathologist including well- (n = 18), moderately (n = 35), and poorly differentiated (n = 47) lesions. A panel of 52 microsatellite markers representing 26 chromosomal regions commonly altered in breast cancer was used to assess patterns of AI.
  
  
  RESULTS
  The overall frequency of AI increased significantly (P < .001) with increasing grade (well differentiated, 12%; moderately differentiated, 17%; poorly differentiated, 26%). Levels of AI were not significantly different between well- and moderately differentiated grades of disease but were significantly higher (P < .0001) in poorly differentiated compared with well- or moderately differentiated disease. No statistically significant differences in patterns of AI were detected between well- and moderately differentiated disease; however, AI occurred significantly more frequently (P < .05) in high-grade lesions at chromosomes 6q25-q27, 8q24, 9p21, 13q14, and 17p13.1, and significantly more frequently in low-grade lesions at chromosome 16q22.3-q24.3.
  
  
  CONCLUSIONS
  The inability to discriminate DCIS at the genetic level suggests that grades 1 and 2 DCIS may represent a single, non-high-grade form of DCIS, whereas poorly differentiated DCIS seems to be a genetically more advanced disease that may represent a discrete disease entity, characterized by a unique spectrum of genetic alterations.
authors.affiliation: Clinical Breast Care Project, Windber Research Institute, 620 Seventh Street, Windber, PA 15963, USA. r.ellsworth@wriwindber.org
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Ellsworth
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Ellsworth
authors.forename: Brad
authors.initials: B
authors.lastname: Love
authors.forename: Heather L
authors.initials: HL
authors.lastname: Patney
authors.forename: Laurel R
authors.initials: LR
authors.lastname: Hoffman
authors.forename: Jennifer
authors.initials: J
authors.lastname: Kane
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hooke
authors.forename: Craig D
authors.initials: CD
authors.lastname: Shriver
mesh_terms: D022981:Allelic Imbalance; D001943:Breast Neoplasms / Q000175:diagnosis / Q000235:genetics*; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis / Q000235:genetics*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000175:diagnosis / Q000235:genetics*; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000648:ultrastructure*; D004247:DNA / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D042822:Genomic Instability; D006801:Humans; D008875:Middle Aged; D015995:Prevalence; D011379:Prognosis
chemical_list: D004273:DNA, Neoplasm; D004247:DNA