Correlation of levels and patterns of genomic instability with histological grading of DCIS

Rachel E. Ellsworth*, Darrell L. Ellsworth, Brad Love, Heather L. Patney, Laurel R. Hoffman, Jennifer Kane, Jeffrey A. Hooke, Craig D. Shriver

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations


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.

Original languageEnglish
Pages (from-to)3070-3077
Number of pages8
JournalAnnals of Surgical Oncology
Issue number11
StatePublished - Nov 2007
Externally publishedYes


  • Allelic imbalance
  • Ductal carcinoma-in-situ
  • Genomic instability
  • Histological grade
  • Tumor classification


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