Cyclin D1b 在人乳腺癌中的表达及其与 cyclin D1a 的共表达与不良预后相关。
Cyclin D1b in human breast carcinoma and coexpression with cyclin D1a is associated with poor outcome.
机构信息
Department of Medicine, University of Pennsylvania, PA, USA.
出版信息
Anticancer Res. 2010 Apr;30(4):1279-85.
BACKGROUND/AIM: Cyclin D1 is a mediator of cell-cycle control that is frequently overexpressed in primary ductal breast carcinomas, but its role is controversial. A polymorphism in the CCND1 gene, G870A, results in an aberrantly spliced protein (cyclin D1b) lacking the Thr-286 phosphorylation site necessary for nuclear export. Studies of murine fibroblasts have shown that although overexpression of canonical cyclin D1 (cyclin D1a) alone is not sufficient to drive malignant transformation, expression of nuclear cyclin D1b is oncogenic. Our objectives were to determine whether cyclin D1b is expressed in human breast carcinomas and to characterize the relationship of this protein to both cyclin D1a and clinical outcome in breast cancer patients.
PATIENTS AND METHODS
We performed a prospective cohort study of women with early-stage breast cancer and analyzed cyclin D1a and D1b expression in primary breast tumor sections. Expression was tested for correlation with other breast cancer prognostic factors and clinical outcome, including recurrence or death.
RESULTS
A total of 118 patients were included in this analysis, with a median follow-up of 44 months. Cyclin D1b was expressed in 26% of tumors and cyclin D1a was overexpressed in 27%; co-expression occurred in 4%. Cyclin D1a and/or D1b expression were not significantly associated with estrogen or progesterone receptor negativity, Her2 overexpression, young age, lymph node positivity, high tumor grade, nor large tumor size. The risk of recurrence was higher in those co-expressing D1a and D1b compared to the expression of either alone (relative risk=5.3, 95% confidence interval 1.27 to 22.1, p=0.02). The hazard ratio for those with co-expression compared with those without was 6.05 (p=0.04).
CONCLUSION
Expression of cyclin D1b occurs in primary human breast carcinomas and its coexpression with cyclin D1a may be a marker for increased recurrence risk, independently of other factors.
背景/目的：细胞周期蛋白 D1 是细胞周期调控的介质，在原发性乳腺导管癌中经常过表达，但它的作用存在争议。CCND1 基因中的一个 G870A 点突变导致异常剪接蛋白（cyclin D1b）的产生，该蛋白缺失了核输出所必需的 Thr-286 磷酸化位点。对鼠成纤维细胞的研究表明，尽管单独过表达经典的细胞周期蛋白 D1（cyclin D1a）不足以驱动恶性转化，但核细胞周期蛋白 D1b 的表达是致癌的。我们的目的是确定 cyclin D1b 是否在人乳腺癌中表达，并描述这种蛋白与 cyclin D1a 以及乳腺癌患者临床结果的关系。
患者和方法
我们对早期乳腺癌患者进行了前瞻性队列研究，并分析了原发性乳腺癌组织切片中 cyclin D1a 和 D1b 的表达。检测了其与其他乳腺癌预后因素和临床结果（包括复发或死亡）的相关性。
结果
共有 118 例患者纳入本研究，中位随访时间为 44 个月。26%的肿瘤表达 cyclin D1b，27%的肿瘤过表达 cyclin D1a，4%的肿瘤同时过表达这两种蛋白。cyclin D1a 和/或 D1b 的表达与雌激素或孕激素受体阴性、Her2 过表达、年龄较小、淋巴结阳性、高肿瘤分级、肿瘤较大无关。与单独表达 cyclin D1a 或 D1b 相比，同时表达 cyclin D1a 和 D1b 的患者复发风险更高（相对风险=5.3，95%置信区间 1.27 至 22.1，p=0.02）。与无表达者相比，同时表达者的风险比为 6.05（p=0.04）。
结论
cyclin D1b 在原发性人乳腺癌中表达，与 cyclin D1a 共同表达可能是复发风险增加的标志物，独立于其他因素。
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