Elevated expression levels of NCOA3, TOP1, and TFAP2C in breast tumors as predictors of poor prognosis

BACKGROUND Amplification of DNA in certain chromosomal regions plays a crucial role in the development and progression of human malignancies, specifically when protooncogenic target genes within those amplicons are overexpressed. Comparative genomic hybridization studies have revealed frequent amplification at 20q in primary breast tumors. The aim of the current study was to identify specific genes in the 20q amplicon that were likely to have clinical significance. METHODS The authors examined 38 primary breast tumors by using a quantitative real-time reverse transcription–polymerase chain reaction assay to determine expression levels of 18 potential targets for amplification events involving 20q. Potential correlations between elevated expression of the genes in question and clinicopathologic parameters or clinical outcomes were analyzed. RESULTS Elevated expression of NABC1 was significantly associated with positive estrogen (P < 0.001) and progesterone (P = 0.027) receptors in breast tumors, and high expression of PTK6 was significantly correlated with positive estrogen receptor status (P = 0.022) and postmenopausal status (P = 0.008). Patients whose tumors showed elevated expression of NCOA3 (AIB1) had significantly shorter disease-free (P = 0.017) and overall (P = 0.0021) survival times after surgery than did other patients with breast tumors. Reduced disease-free survival, but not reduced overall survival, was associated with high expression of TOP1 (P = 0.035) and TFAP2C (P = 0.035). CONCLUSIONS TOP1, TFAP2C, and (particularly) NCOA3 may be prognostic indicators for patients with breast tumors. Cancer 2003;98:18–23. © 2003 American Cancer Society. DOI 10.1002/cncr.11482