Copy number analysis of ductal carcinoma in situ with and without recurrence

Mod Pathol. 2015 Sep;28(9):1174-84. doi: 10.1038/modpathol.2015.75. Epub 2015 Jun 19.

Abstract

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer and a frequent mammographic finding requiring treatment. Up to 25% of DCIS can recur and half of recurrences are invasive, but there are no reliable biomarkers for recurrence. We hypothesised that copy number aberrations could predict likelihood of recurrence. We analysed a cohort of pure DCIS cases treated only with wide local excision for genome-wide copy number and loss of heterozygosity using Affymetrix OncoScan MIP arrays. Cases included those without recurrence within 7 years (n = 25) and with recurrence between 1 and 5 years after diagnosis (n = 15). Pure DCIS were broadly similar in copy number changes compared with invasive breast cancer, with the consistent exception of a greater frequency of ERBB2 amplification in DCIS. There were no significant differences in age or ER status between the cases with a recurrence vs those without. Overall, the DCIS cases with recurrence had more copy number events than the DCIS without recurrence. The increased copy number appeared non-random with several genomic regions showing an increase in frequency in recurrent cases, including 20 q gain, ERBB2 amplification and 15q loss. Copy number changes may provide prognostic information for DCIS recurrence, but validation in additional cohorts is required.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Breast Neoplasms / genetics*
  • Carcinoma, Intraductal, Noninfiltrating / genetics*
  • Female
  • Gene Dosage
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics*
  • Oligonucleotide Array Sequence Analysis
  • Polymerase Chain Reaction