可手术乳腺癌中细胞周期调节因子的蛋白表达模式
Protein expression patterns of cell cycle regulators in operable breast cancer.
作者信息
Zagouri Flora, Kotoula Vassiliki, Kouvatseas George, Sotiropoulou Maria, Koletsa Triantafyllia, Gavressea Theofani, Valavanis Christos, Trihia Helen, Bobos Mattheos, Lazaridis Georgios, Koutras Angelos, Pentheroudakis George, Skarlos Pantelis, Bafaloukos Dimitrios, Arnogiannaki Niki, Chrisafi Sofia, Christodoulou Christos, Papakostas Pavlos, Aravantinos Gerasimos, Kosmidis Paris, Karanikiotis Charisios, Zografos George, Papadimitriou Christos, Fountzilas George
机构信息
Department of Clinical Therapeutics, Alexandra Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, Greece.
Department of Pathology, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece.
出版信息
PLoS One. 2017 Aug 10;12(8):e0180489. doi: 10.1371/journal.pone.0180489. eCollection 2017.
BACKGROUND-AIM: To evaluate the prognostic role of elaborate molecular clusters encompassing cyclin D1, cyclin E1, p21, p27 and p53 in the context of various breast cancer subtypes.
METHODS
Cyclin E1, cyclin D1, p53, p21 and p27 were evaluated with immunohistochemistry in 1077 formalin-fixed paraffin-embedded tissues from breast cancer patients who had been treated within clinical trials. Jaccard distances were computed for the markers and the resulted matrix was used for conducting unsupervised hierarchical clustering, in order to identify distinct groups correlating with prognosis.
RESULTS
Luminal B and triple-negative (TNBC) tumors presented with the highest and lowest levels of cyclin D1 expression, respectively. By contrast, TNBC frequently expressed Cyclin E1, whereas ER-positive tumors did not. Absence of Cyclin D1 predicted for worse OS, while absence of Cyclin E1 for poorer DFS. The expression patterns of all examined proteins yielded 3 distinct clusters; (1) Cyclin D1 and/or E1 positive with moderate p21 expression; (2) Cyclin D1 and/or E1, and p27 positive, p53 protein negative; and, (3) Cyclin D1 or E1 positive, p53 positive, p21 and p27 negative or moderately positive. The 5-year DFS rates for clusters 1, 2 and 3 were 70.0%, 79.1%, 67.4% and OS 88.4%, 90.4%, 78.9%, respectively.
CONCLUSIONS
It seems that the expression of cell cycle regulators in the absence of p53 protein is associated with favorable prognosis in operable breast cancer.
背景-目的：评估包含细胞周期蛋白D1、细胞周期蛋白E1、p21、p27和p53的精细分子簇在不同乳腺癌亚型中的预后作用。
方法
在1077例来自参与临床试验的乳腺癌患者的福尔马林固定石蜡包埋组织中，采用免疫组织化学方法评估细胞周期蛋白E1、细胞周期蛋白D1、p53、p21和p27。计算各标志物的杰卡德距离，并将所得矩阵用于进行无监督层次聚类，以识别与预后相关的不同组。
结果
管腔B型和三阴性（TNBC）肿瘤分别呈现细胞周期蛋白D1表达的最高和最低水平。相比之下，TNBC经常表达细胞周期蛋白E1，而雌激素受体阳性肿瘤则不表达。细胞周期蛋白D1缺失预示着较差的总生存期，而细胞周期蛋白E1缺失则预示着较差的无病生存期。所有检测蛋白的表达模式产生了3个不同的簇；（1）细胞周期蛋白D1和/或E1阳性且p21表达中等；（2）细胞周期蛋白D1和/或E1以及p27阳性，p53蛋白阴性；以及，（3）细胞周期蛋白D1或E1阳性，p53阳性，p21和p27阴性或中等阳性。簇1、2和3的5年无病生存率分别为70.0%、79.1%、67.4%，总生存率分别为88.4%、90.4%、78.9%。
结论
在可手术乳腺癌中，似乎在没有p53蛋白的情况下细胞周期调节因子的表达与良好预后相关。
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