Chromosome 17 Aneusomy is Associated with Poor Prognostic Factors in Invasive Breast Carcinoma

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Abstract
Aberrations of chromosome 17 are common in breast cancer. Fluorescence in situ hybridization (FISH) enables gene or chromosome copy number to be assessed in situ in archival tissues and related to morphology and clinical outcome. In this study direct labeled DNA probes for the chromosome 17 alpha satellite and the HER2/neu gene were applied simultaneously to 5 micron sections of 214 formalin-fixed paraffin-embedded invasive primary breast carcinomas. A high proportion (54%) of invasive breast carcinomas displayed aneusomy of chromosome 17. Polysomy 17 correlated with multiple copies of HER2/neu (p = HER2/neu amplification. Eighty-six patients without HER2/neu amplification had aneusomy 17. Fifty-eight of the 86 patients that had aneusomy 17 had high HER2/neu copy number. Twelve patients with normal copy number for chromosome 17 had amplification of HER2/neu and 30 patients had amplification of HER2/neu with aneusomy 17. Aneusomy 17 was associated with grade 3 carcinoma (p = 0.008), ER negativity (p = 0.0032) and a Nottingham prognostic index of greater than 5.4 (p = 0.039) but was not associated with survival by univariate analysis. In conclusion, the determination of chromosome 17 copy number should be incorporated in assessment of HER2/neu status, as this will give an accurate measure of amplification of HER2/neu and may also be helpful in determining suitability for breast carcinoma trials.