CEP17 “Polysomy” (CEP17P): Definition and Impact on HER2 Copy Number (CN) in Breast Carcinoma
Kristine Astvatsaturyan, James Mirocha, Shikha Bose. Cedars-Sinai Medical Center, Los Angeles, CA
Background: CEP17P is a frequent finding in breast cancer and complicates the interpretation of HER2 amplification results. Its reported frequency and definition varies considerably. Various studies have used mean cut off values between 2.1 to 3. Recent reports suggest that CEP17P results from centromeric amplification and is not linked to true polysomy of chromosome17. Therefore its use in the evaluation of HER2 status may provide misleading information. This study aims at defining CEP17P and determining its relationship with HER2 CN.
Design: 235 consecutive cases of invasive breast cancer diagnosed between 4/1-8/30/10 were reviewed. Fixation of breast tissue and evaluation of prognostic markers were in accordance with 2007 CAP guidelines. Mean CEP17 CN/cell was recorded to determine incidence and relationship to various prognostic markers including tumor size, tumor grade, lymph node metastasis, ER, PR, Ki-67, and HER2 expression, amplification and presence of genetic heterogeneity (GH). Spearman correlation, Fisher exact test, Wilcoxon rank sum test and linear regression analyses were performed. A two sided p-value of 0.05 was considered significant.
Results: Mean CEP17 CN/cell varied from 1.1 to 8.7 (median 2.1). Values of ≥2.2 were noted in 44% (104/235) cases while 15% (36/235) demonstrated ≥3 CEP17/cell. A significant positive correlation between CEP17 CN and lymph node metastasis, proliferation rate (Ki67), mean HER2 CN/cell and HER2 GH and a significant negative correlation with ER and PR levels was noted. These associations were maintained at CEP17 CN of ≥2.2 (Wilcoxon rank sum test). The positive correlation observed between CEP17 and HER2 CN was seen in cases with ≤6 HER2 copies/cell representing cases without true HER2 amplification (Figure 1, blue line). No correlation was observed in cases with true amplification (Figure 1, purple line)
Conclusions: CEP17 CN/cell of ≥2.2 is observed in 44% and ≥3 in 15% of breast cancers.
Correlation with adverse pathological features is noted at CEP17 CN/cell of ≥2.2 indicating that this may be the appropriate definition of CEP17 polysomy.
Strong correlation is noted between CEP17 and HER2 CN of ≤6 indicating that CEP17P is associated with concurrent increase in HER2 CN in cases without true HER2 amplification.
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 47, Wednesday Morning