Polysomy of Chromosome 17 in Breast Cancer.

Abstract

Abstract Purpose: Polysomy of chromosome 17 is frequently described in breast cancer, but firm definition of polysomy is lacking. We have used normal breast tissue to define the ploidy levels in the truncated nuclei of cut sections based on standard cytogenetic definition of ploidy in whole nuclei. Data from patients with invasive breast cancer enrolled in a randomized clinical trial was used to investigate the effect of polysomy of centromere 17 on patient survival. (Ejlertsen B et al., Eur J Cancer 2007:43:877-84).Material and methods: Fluorescence in situ hybridization (FISH) with TOP2A/CEN-17 was performed on 120 normal breast specimens. Centromere 17 (CEN-17) measurements from matching HER2/CEN-17 and TOP2A/CEN-17 FISH data was available from 649 patients from a previously published biomarker study (Knoop A et. al., J Clin Oncol 2005;23:7483-90).Results: Two thirds of the tumors had an average number of CEN-17 signals below two and 10% had more than three average CEN-17 signals. Monosomy (<1.25 CEN-17/nucleus) of centromere 17 was observed in 8% of the tumors, 60% of the samples were diploid (1.26-2.09 CEN-17/nucleus), 22% triploid (2.10-2.93 CEN-17/nucleus), 5% tetraploid (2.94-3.77 CEN-17/nucleus) and 5% of the tumors had higher ploidy level (>3.78 CEN-17/nucleus). In the aneuploid tumors and especially in the highly polyploidy tumors, amplification is the most frequent event in the HER2 assay whereas deletions increased with the ploidy level in TOP2A assay. Increasing ploidy was associated with decreased overall survival (P=0.0001), but multivariate analysis showed that polyploidy was not an independent prognostic factor neither predictive for treatment outcome.Conclusion: Polysomy 17 is a rare event in tumor samples from patients, but correlate to HER2 amplification and TOP2A deletion. However, inclusion of a reference probe is necessary if deletions are to be revealed and to avoid false positive amplified cases with a high proportion of dividing cells or a doubling of the DNA content. Very high polyploidy is associated with poor survival but is not an independent prognostic factor when other prognostic factor are included in a multivariate analysis. In this large clinical study, polysomy 17 was neither an independent prognostic nor predictive marker. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 4035.