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Markers of Increased Risk in Pre-Invasive Breast Cancer

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Annual summary rept. 1 Jan 2002-1 Jan 2003

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The risk of recurrence and progression of ductal carcinoma in-situ DCIS of the breast is best designated by morphological indicators including the presence of necrosis. To identify molecular alterations underlying this morphological feature we have compared gene expression within a cohort of 6 cases of DCIS with necrosis DCIS necrosis and 4 cases without necrosis DCIS necrosis- using microdissection and cDNA microarray. A set of 69 cDNAs, from a group of 1,181, was identified that were consistently differentially expressed. Amongst this set, the mRNA for angio-associated migratory cell protein AAMP and a serine threonine protein kinase, nuclear Dbf2 related NDR, were consistently higher in DCIS necrosis and were also found to be overexpressed in the T47D breast cancer cell line subjected to hypoxia. A significant differential expression P0.0095 was confirmed for AAMP by quantitative reverse transcriptase polymerase chain reaction RT-PCR. Further study of AAMP by RT-PCR and in situ hybridization analysis of 37 cases of DCIS also confirmed that a higher AAMP mRNA expression tended to be associated with high-grade nuclear morphology and necrosis. The present study shows that while levels of gene expression are mostly similar between morphologically different DCIS, consistent differences in expression of a subset of genes can be identified between DCIS with and without necrosis.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Anatomy and Physiology
  • Medicine and Medical Research

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