Gillett C, Smith P, Gregory W, Richards M, Millis R, Peters G, Barnes D
Clinical Oncology Unit, Guy's Hospital, London, UK.
Int J Cancer. 1996 Apr 22;69(2):92-9. doi: 10.1002/(SICI)1097-0215(19960422)69:2<92::AID-IJC4>3.0.CO;2-Q.
We have used immunohistochemical staining to assess the expression of cyclin D1 in formalin-fixed sections of 345 breast carcinomas, dating back 20 years. Clinical follow-up data were available on all patients. Approximately 50% of the tumours showed excessive nuclear staining for cyclin D1 as compared with normal epithelium. Some tumours showed strong cytoplasmic staining in the absence of nuclear staining, and around 25% of the tumours were judged to be negative for nuclear cyclin D1. Contrary to expectations, moderate/strong staining for cyclin D1 was associated with improved relapse-free and overall survival relative to patients whose tumours stained weakly or negatively. Conversely, tumours that were considered negative for cyclin D1 staining had an adverse prognosis, and the poor outcome was further accentuated if the tumours were also oestrogen receptor-negative. A possible explanation for our findings is that tumours in which cyclin D1 levels are abnormally low may have sustained mutations in other genes, such as RBI and that it is this abnormality that has the more significant impact on survival from breast cancer.
我们采用免疫组化染色法评估了345例乳腺癌福尔马林固定切片中细胞周期蛋白D1的表达情况，这些病例可追溯到20年前。所有患者均有临床随访数据。与正常上皮相比，约50%的肿瘤细胞周期蛋白D1核染色过度。一些肿瘤在无核染色的情况下显示强细胞质染色，约25%的肿瘤被判定为细胞周期蛋白D1核染色阴性。与预期相反，相对于肿瘤弱染色或阴性的患者，细胞周期蛋白D1中度/强染色与无复发生存期和总生存期改善相关。相反，细胞周期蛋白D1染色被认为阴性的肿瘤预后不良，如果肿瘤同时也是雌激素受体阴性，则不良结局会进一步加重。对我们研究结果的一种可能解释是，细胞周期蛋白D1水平异常低的肿瘤可能在其他基因（如RBI）中存在持续突变，正是这种异常对乳腺癌生存产生了更显著的影响。
