[225] Chromosome 17 Polysomy: Correlation with Histological Parameters and HER2/Neu Gene Amplification

Maria Orsaria, Sihem Khelifa, Natalia Buza, Anitha Kamath, Pei Hui. Yale University, New Haven, CT; Azienda Ospedaliero-Universitaria S. Maria della Misericordia, Udine, Italy

Background: HER2 gene amplification is present in the majority of invasive breast carcinomas that have HER2 protein overexpression. A subset of breast cancers harbor an increased chromosome 17 copy number (polysomy 17), frequently associated with comparable HER2 copy number increase. We investigated the clinicopathologic significance of polysomy 17 in correlation with various histological parameters and HER2 gene amplification.
Design: Surgical specimens of 266 consecutive cases of primary invasive breast carcinomas were selected from a single tertiary medical center. HER2 gene status and chromosome 17 copy numbers were assessed by dual-color fluorescent in situ hybridization (FISH). Chromosome 17 polysomy was determined by the presence of ≥3 average CEP17 signals per average nucleus of 30 invasive tumor cells.
Results: Overall 63 tumors (23.7%, 63/266) harbored polysomy 17. Carcinomas with polysomy 17 were associated with adverse histological indicators including high histological grade, high nuclear grade, poor Nottingham Prognostic Index, advanced local tumor extent (pT4) and progesterone receptor negativity. Polysomy 17 was more frequently observed in HER2 unamplified (71.4%) than in HER2 amplified cases (23.8%). However, polysomy cases were more often HER2 3+ by immunohistochemistry (17.5%, 11/63) than the nonpolysomy cases (5.9%,12/203). Five cases (2%, 5/266) had HER2 protein overexpression (3+ by immunohistochemistry) but failed to demonstrate the HER2 gene amplification by FISH, none of which had more than 6 CEP17 signals per average nucleus.
Conclusions: In conclusion, polysomy 17 is significantly correlated with several adverse histological parameters including high histological grade, high nuclear grade, poor Nottingham prognostic index, advanced local tumor extent and PR negativity. Polysomy 17 is common to both HER2 amplified and unamplified tumors. In the absence of the gene amplification, HER2 protein overexpression may be explained by other mechanisms including the transcription upregulation and polysomy 17.
Category: Breast

Wednesday, March 21, 2012 1:00 PM

Poster Session VI # 9, Wednesday Afternoon

 

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