Prognostic and predictive value of 16p12.1 and 16q22.1 copy number changes in human breast cancer

The present study investigated DNA copy number changes mapping to the p and q arms of chromosome 16 in breast cancer with the goal to determine their potential in identifying breast cancer patients with poor prognosis. We identified the minimal overlapping regions on chromosome 16 that are commonly deleted and amplified in breast tumors. Fluorescence in situ hybridization was used to screen a custom-made breast carcinoma tissue microarray representing all tumor grades, in order to detect DNA copy number changes mapping to 16p12.1 and 16q22.1. We generated 16q/16p ratios for each patient and examined the correlation between DNA copy number alterations and the patients' clinical and pathological parameters. We observed lower q/p ratios in grade I invasive carcinomas, compared with grade III carcinomas, which consistently showed high q/p ratios (P < 0.0091 and 0.0075). In addition, age adjusted for grade analysis revealed that tumors from younger patients (<45 yr) had significantly higher q/p ratios, suggesting that in younger individuals those tumors might be more aggressive (P < 0.0001). The finding that higher q/p ratios occur in younger patients offers a tool to identify high-risk individuals most likely to proceed to high grade.