AMPLIFICATION OF CHROMOSOMAL REGION 20Q13 IN INVASIVE BREAST-CANCER -PROGNOSTIC IMPLICATIONS

Amplification of the chromosome 20q13 region was recently discovered i n breast cancer by comparative genomic hybridization and subsequently further defined by fluorescence in situ hybridization with specific pr obes. The target gene of the amplification remains unknown, Here, fluo rescence in situ hybridization with a cosmid probe for the minimal reg ion of amplification (RMC20C001) was used to study 20q13 amplification in 132 primary breast carcinomas and 11 metastases, The size of the a mplicon was studied with four flanking probes, Thirty-eight (29%) prim ary tumors and 3 (27%) metastases showed increased copy number of the RMC20C001 probe (> 1.5-fold relative to the p-arm control), Nine (6.8% ) of the primary tumors were highly (> 3-fold) amplified, Although the size and location of the amplified region varied from one tumor to an other, only the RMC20C001 probe was consistently amplified, 20q13 ampl ification was significantly associated with a high histological grade (P = 0.01), DNA aneuploidy (P = 0.01), and high S-phase fraction (P = 0.0085). High-level amplification was also associated with short disea se-free survival of patients with node-negative breast cancer (P = 0.0 02), We conclude that high-level 20q13 amplification may be an indicat or of poor clinical outcome in node-negative breast cancer and that th is chromosomal region is likely to contain a gene with an important ro le in breast cancer progression, A large definitive study is warranted to assess the independent prognostic value of 20q13 amplification.