Department of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK.
Int J Cancer. 2010 Jul 15;127(2):355-60. doi: 10.1002/ijc.25034.
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.
CCND1 编码参与 G1/S 细胞周期转换的细胞周期蛋白 D1 蛋白。在乳腺癌中，需要阐明 CCND1 扩增的机制、细胞周期蛋白 D1 蛋白表达与关键临床标志物雌激素受体 (ER) 和 HER2 之间的关系。对 93 名女性的原发性浸润性乳腺癌组织微阵列进行了荧光原位杂交以评估 CCND1 扩增，并用免疫组织化学评估了 cyclin D1 蛋白的过表达。在 93 例癌症中有 27/93（30%）存在 CCND1 扩增，59/93（63%）的癌症存在 cyclin D1 蛋白过表达。CCND1 扩增与 cyclin D1 蛋白过表达显著相关（p<0.001；Fisher 确切检验），CCND1 扩增和 cyclin D1 蛋白表达均与雌激素受体（ER）表达相关（p=0.003 和 p<0.001；Fisher 确切检验）。CCND1 扩增或 cyclinD1 表达均与肿瘤大小、病理淋巴结状态或 HER2 扩增无关，但高 CCND1 扩增（拷贝数增益（CNG）≥8）与高肿瘤分级相关（p=0.005；卡方检验 7.915，2 自由度）和诺丁汉预后指数（p=0.001；2 样本 t 检验）预后较差。高 CCND1 扩增（CNG≥8）可能会识别出一组预后不良的 ER 阳性乳腺癌患者，这些患者应考虑额外的治疗。
