Down-regulation of beta(1C) integrin in breast carcinomas correlates with high proliferative fraction, high histological grade, and larger size.
Down-regulation of beta(1C) integrin in breast carcinomas correlates with high proliferative fraction, high histological grade, and larger size.
复制标题
乳腺癌中 β(1C) 整合素的下调与高增殖分数、高组织学分级和较大尺寸相关。
DOI：
10.1016/s0002-9440(10)64716-5
复制
发表时间：
2000
期刊：
影响因子：
--
通讯作者：
Viale,G
中科院分区：
文献类型：
--
作者：
Manzotti,M;Dell'Orto,P;Maisonneuve,P;Fornaro,M;Languino,LR;Viale,G
β1整合素是整合素β1亚家族的非剪接形式，已被证明在体外抑制细胞增殖。使用亲和纯化兔抗体，我们研究了283例未经治疗的乳腺癌，目的是确定β1在这些肿瘤中的实际表达率，并确定其病理相关性。免疫印迹和逆转录聚合酶链反应实验也在选定的病例中进行，以证实免疫细胞化学的发现。总体而言，114例（40.3%）患者β1免疫反应性下调（即在肿瘤细胞中表达低于50%）。在乳腺癌中，β1表达下调与肿瘤分级、增殖分数（用mb -1单克隆抗体Ki-67免疫染色评价）、雌激素和孕激素受体状态、肿瘤大小（pT分类）显著相关，与淋巴结状态不显著相关。在同时拟合所有可用指标的多变量分析中，肿瘤分级（P = 0.004）、Ki-67免疫标记（P = 0.01）和pT分类（P = 0.04）与β 1c免疫反应性显著相关。虽然目前这一系列患者的随访时间较短（2-3年），无法进行生存分析，但β1表达与肿瘤大小、分级和增殖分数的相关性，以及其作为p27kip1上游调节因子的作用，使这种整合素变体可能成为浸润性乳腺癌的一种新的预后参数。
β1Cintegrin is an unspliced form of the integrin β1subfamily, which has been shown to inhibit cell proliferation in vitro. Using an affinity-purified rabbit antibody, we have investigated 283 previously untreated breast carcinomas, with the aim of ascertaining the actual prevalence of β1Cexpression in these tumors and of defining its pathological correlates. Immunoblotting and reverse transcriptase-polymerase chain reaction experiments have also been performed in selected cases, to confirm the immunocytochemical findings. Overall, β1Cimmunoreactivity was down-regulated (ie, expressed in < 50% of the neoplastic cells) in 114 cases (40.3%). Down-regulation of β1Cexpression in breast carcinomas correlated significantly with the tumor grade, the proliferative fraction (as evaluated by Ki-67 immunostaining with the MIB-1 monoclonal antibody), the estrogen and progesterone receptor status, and the tumor size (pT classification) and marginally with the node status. In a multivariate analysis with all available measures fitted simultaneously, tumor grade (P = 0.004), Ki-67 immunolabeling (P = 0.01), and pT categories (P = 0.04) were significantly associated with β1Cimmunoreactivity. Although the short follow-up time (2–3 years) of the current series of patients does not allow the performance of survival analyses, the correlation of β1Cexpression with tumor size, grade, and proliferative fraction and its alleged role as an upstream regulator of p27kip1make this integrin variant a likely novel prognostic parameter for invasive carcinomas of the breast.