Expression of Cyclin D1, MIB-1 (Ki-67) and Estrogen Receptor (ER) in Flat Epithelial Atypia (FEA)
M Chivukula, G Carter, DJ Dabbs. Magee Women's Hospital of UPMC, Pittsburgh, PA
Background: The clinical significance of FEA in the literature is beginning to emerge; recent studies (kunju et al, chivukula et al) have shown a significant upstaging in FEA up to 14%. Though very few papers have defined FEA, at times as having “bland nuclear cytology” sometimes difficult to differentiate these lesions from benign CCC. In the pursuit to find useful markers that can recognize these lesions from benign CCC, we have selected three markers. Literature on Cyclin D1, a cell cycle regulatory protein, is meagre in relation to breast carcinoma, although alterations were seen in apocrine metaplasia (APM).This protein is seen in various lymphomas suggesting cellular instability contributing to increased susceptibility to carcinogenesis. The aim of the study is to study the expression of Cyclin D1, MIB-1(ki-67) and ER in FEA and CCC.
Design: Twenty (20) cases of pure FEA cases were selected. We defined FEA as per the WHO criteria. Positive cyclin D1 expression is defined as strong nuclear staining in >20% of cells (colombo et al). A proliferation index (PI) is calculated for MIB-1(ki67) a nuclear stain as low- <10%, moderate 11-25%, high 26-50%, and high>50%. For ER, a 10% or more “nuclear “staining of the tumor cells was considered “positive”A cumulative “H score” is derived based on proportionality (PS) and intensity scores (IS) [0 negative, 1-150 low, 151-250 intermediate, 250-300 high].
Results: A strong ER expression was seen in 100% (18/18) FEA cases with a mean H score of 195 (range 140-220); a low MIB -1 (ki-67) staining was seen in all cases with a mean proliferation index of 3.2 A strong intense nuclear staining of Cyclin D 1 was seen in up to 95% (19/20) of cases. In the adjacent CCC, a strong ER expression was seen in 100% (18/18) of cases. However there was overtly less cyclin D1 staining in 100% (20/20) of cases. MIB-1 (ki-67) was absent /weak staining with a mean proliferation index of 1.0.
Conclusions: 1. FEA are proliferating lesions as demonstrated by increased MIB-(ki-67) in comparison to CCC. 2. Increased expression of Cyclin D1 in FEA suggests alterations that may contribute to the role of these lesions in the low grade breast cancer pathway. 3. A high expression of ER in these lesions suggests their possible “precursor” role in the predisposition of women to develop invasive breast carcinoma.4. A combination of these markers can be used to distinguish these lesions from benign CCC.
Tuesday, March 23, 2010 1:00 PM
Poster Session IV # 18, Tuesday Afternoon