CCND1 amplification in breast cancer -associations with proliferation, histopathological grade, molecular subtype and prognosis

Abstract

CCND1 is located on 11q13. Increased CCND1 copy number (CN) in breast cancer (BC) is associated with high histopathological grade, high proliferation, and Luminal B subtype. In this study of CCND1 in primary BCs and corresponding axillary lymph node metastases (LNM),we examine associations between CCND1 CN in primary BCs and proliferation status, molecular subtype, and prognosis. Furthermore, we studied associations between CCND1 CN and CNs of FGFR1 and ZNF703, both of which are located on 8p12. Fluorescence in situ hybridization probes for CCND1 and chromosome 11 centromere were used on tissue microarrays comprising 526 BCs and 123 LNM. We assessed associations between CCND1 CN and tumour characteristics using Pearson’s χ2 test, and estimated cumulative risks of death from BC and hazard ratios in analysis of prognosis. We found CCND1 CN ≥ 4 < 6 in 45 (8.6%) tumours, and ≥ 6 in 42 (8.0%). CCND1 CN (≥ 6) was seen in all molecular subtypes, most frequently in Luminal B (HER2−) (20/126; 16%). Increased CCND1 CN was associated with high histopathological grade, high Ki-67, and high mitotic count, but not prognosis. CCND1 CN ≥ 6 was accompanied by CN increase of FGFR1 in 6/40 cases (15.0%) and ZNF703 in 5/38 cases (13.2%). Three cases showed CN increase of all three genes. High CCND1 CN was most frequent in Luminal B (HER2−) tumours. Good correlation between CCND1 CNs in BCs and LNM was observed. Despite associations between high CCND1 CN and aggressive tumour characteristics, the prognostic impact of CCND1 CN remains unresolved.