Columnar Cell Hyperplasia with Atypia Is Biologically Similar to Ductal Carcinoma In Situ, Not Columnar Cell Hyperplasia
Souzan Sanati, Craig Allred. Washington University in St Louis, School of Medicine, St Louis, MO
Background: Columnar cell hyperplasia with atypia (CCH-A) is diagnostically challenging on H&E-stained slides. Although its clinical significance is unclear, compelling evidence suggests that it is associated with a high-risk for developing breast cancer, and may be a direct precursor. We hypothesize that CCH-A is biologically different than columnar cell hyperplasia without atypia (CCH), and similar to low-grade ductal carcinoma in situ (DCIS) which, if true, could provide novel tools (i.e. biomarkers) to improve the diagnosis of CCH-A. The purpose of this study was to compare molecular features of CCH, CCH-A, and DCIS at the RNA and protein levels, predicting that there are unique features shared between CCH-A and DCIS.
Design: Gene expression profiling was performed using microarrays (Affymetrix U133-A) utilizing RNA isolated from luminal cells within normal terminal duct lobular units (TDLUs), CCH (n=8) and DCIS (n=11) obtained by laser-capture microdissection. Selected transcripts expressed at significantly different levels are being re-evaluated at the protein level by immunohistochemistry on independent samples of TDLUs, CCH, CCH-A, and DCIS.
Results: Microarray analyses identified a large number of significantly differentially expressed gene transcripts (representative examples in Table 1):
|Gene||TDLU vs CCH (fold change)||CCH vs DCIS (fold change)|