High CCND1 amplification identifies a group of poor prognosis women with estrogen receptor positive breast cancer.
CCND1 encodes for the cyclin D1 protein involved in G1/S cell cycle transition. In breast cancer the mechanism of CCND1 amplification, relationship between cyclin D1 protein expression and the key clinical markers estrogen receptor (ER) and HER2 requires elucidation. Tissue microarrays of primary invasive breast cancer from 93 women were evaluated for CCND1 amplification by fluorescent in-situ hybridization and cyclin D1 protein overexpression by immunohistochemistry. CCND1 amplification was identified in 27/93 (30%) cancers and 59/93 (63%) cancers had overexpression of cyclin D1. CCND1 amplification was significantly associated with cyclin D1 protein overexpression (p < 0.001; Fisher's exact test) and both CCND1 amplification and cyclin D1 protein expression with oestrogen receptor (ER) expression (p = 0.003 and p < 0.001; Fishers exact test). Neither CCND1 amplification nor cyclinD1 expression was associated with tumor size, pathological node status or HER2 amplification, but high CCND1 amplification (Copy Number Gain (CNG) > or = 8) was associated with high tumor grade (p = 0.005; chi square 7.915, 2 df) and worse prognosis by Nottingham Prognostic Index (p = 0.001; 2 sample t-test). High CCND1 amplification (CNG > or = 8) may identify a subset of patients with poor prognosis ER-positive breast cancers who should be considered for additional therapy.
Roy
Pankaj G
PG
Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
Pratt
Norman
N
Purdie
Colin A
CA
Baker
Lee
L
Ashfield
Alison
A
Quinlan
Phil
P
Thompson
Alastair M
AM
D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019938:Cyclin D1 / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D046888:Tissue Array Analysis
D014408:Biomarkers, Tumor; C530104:CCND1 protein, human; D011960:Receptors, Estrogen; D019938:Cyclin D1