[271] 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):

Examples of significantly differentially expressed transcript genes in TDLU vs CCH and CCH vs DCIS (all p <0.001)
GeneTDLU vs CCH (fold change)CCH vs DCIS (fold change)
AFP+4X-110X
AREG+10X-12X
CD44--9X
SERPINB5--12X
GABBR1-4X-9X
WIF1--69X


In preliminary IHC studies, expression of CD44 and WIF1 at the protein level was similar across all comparisons. SERPINB5 (maspin) protein expression, which was primarily restricted to myoepithelium in TDLUs, was substantially decreased in CCH-A and DCIS, consistent with the RNA results. SERPINB5 was also expressed (and mislocalized) in the cytoplasm of a varying proportion of CCH-A and DCIS luminal epithelial cells, which was not observed in TDLUs and CCH. Similar IHC studies are ongoing involving additional genes/proteins.
Conclusions: Over 200 differentially expressed gene transcripts (RNA) were identified between CCH and DCIS. Preliminary IHC studies suggest that some of these transcripts (e.g. SERPINB5) are also differentially expressed at the protein level, and that DCIS and CCH-A are similar. Biomarkers of this nature could be useful in improving our ability to diagnose CCH-A.
Category: Breast

Tuesday, March 5, 2013 8:00 AM

Proffered Papers: Section B, Tuesday Morning

 

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